Details of the Researcher

PHOTO

Yoko Tsukita
Section
Tohoku University Hospital
Job title
Assistant Professor
Degree

  • 博士（医学）（東北大学）

Research History 7

  • 2020/05 - Present
    東北大学呼吸器内科 助教

  • 2020/04 - 2020/05
    東北大学呼吸器内科 特任助手

  • 2018/04 - 2020/03
    東北大学呼吸器内科 医員

  • 2012/10 - 2015/03
    宮城県立がんセンター 呼吸器内科

  • 2011/10 - 2012/09
    東北厚生年金病院 呼吸器内科 レジデント

  • 2011/04 - 2011/09
    国立病院機構仙台医療センター 後期臨床研修医

  • 2009/04 - 2011/03
    国立病院機構仙台医療センター 初期臨床研修医

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Education 2

  • Tohoku University　Graduate School of Medicine

    2014/04 - 2018/03

  • Yamagata University　Faculty of Medicine　School of Medicine

    2003/04 - 2009/03

Professional Memberships 7

  • THE JAPANESE CANCER ASSOCIATION

  • 米国臨床腫瘍学会

  • THE JAPAN SOCIETY FOR RESPIRATORY ENDOSCOPY

  • 日本臨床腫瘍学会

  • THE JAPAN LUNG CANCER SOCIETY

  • THE JAPANESE RESPIRATORY SOCIETY

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

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Research Interests 3

  • 胸部腫瘍学

  • 臨床試験

  • 肺癌

Research Areas 1

  • Life sciences / Respiratory medicine /

Awards 3

  1. 日本肺癌学会 若手奨励賞

    2020

  2. ATS Young Investigator

    2019　日本呼吸器学会

  3. 東北大学医学系研究科女子大学院学生奨励賞（七星賞） 優秀賞

    2019

Papers 69

  1. Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile

    Daisuke Narita, Eiji Hishinuma, Risa Ebina-Shibuya, Eisaku Miyauchi, Naomi Matsukawa, Ikuko N. Motoike, Kengo Kinoshita, Seizo Koshiba, Yoko Tsukita, Hirotsugu Notsuda, Nozomu Kimura, Ryota Saito, Hisatoshi Sugiura

    Lung Cancer　108082-108082　2025/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.lungcan.2025.108082 　

    ISSN： 0169-5002

  2. Real-World Outcomes of Subsequent Chemotherapy after Progression Following Chemoradiation and Consolidative Durvalumab Therapy in Locally Advanced Non-small Cell Lung Cancer: An Exploratory Analysis from the CRIMSON Study (HOPE-005). International-journal

    Hayato Kawachi, Motohiro Tamiya, Yuko Oya, Go Saito, Yoshihiko Taniguchi, Hirotaka Matsumoto, Yuki Sato, Taiichiro Otsuki, Hidekazu Suzuki, Yasushi Fukuda, Satoshi Tanaka, Yoko Tsukita, Junji Uchida, Yoshihiko Sakata, Yuki Nakatani, Ryota Shibaki, Daisuke Arai, Asuka Okada, Satoshi Hara, Koichi Takayama, Kazumi Nishino

    Clinical lung cancer　25　(7)　643-652　2024/11

    DOI： 10.1016/j.cllc.2024.07.014 　

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    BACKGROUND: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population. MATERIALS AND METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded. RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy. CONCLUSION: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.

  3. 胸腺腫瘍・まれな腫瘍 進行再発胸腺癌患者に対するレンバチニブの一次治療での有効性および安全性の検討

    芦沼 宏典, 高木 賢人, 齋藤 合, 次富 亮輔, 立原 素子, 宿谷 威仁, 行徳 宏, 坂田 晋也, 毛利 篤人, 三輪 秀樹, 田村 洋輔, 時任 高章, 突田 容子, 小暮 啓人, 益田 武, 田中 洋史, 久保 創介, 鈴木 拓児

    肺癌　64　(5)　426-426　2024/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  4. 初回治療Osimertinibの多施設実態調査(OSI-FACT)における心毒性の検討

    岡田 あすか, 坂田 能彦, 坂田 晋也, 山口 哲平, 田宮 基裕, 鈴木 秀和, 柴木 亮太, 横山 俊秀, 松本 啓孝, 大搗 泰一郎, 佐藤 悠城, 内田 純二, 齋藤 合, 突田 容子, 稲葉 恵, 池田 英樹, 荒井 大輔, 丸山 広高, 原 聡志, 津村 真介, 坂上 拓郎

    肺癌　64　(5)　463-463　2024/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  5. EGFR遺伝子変異陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査(OSI-FACT)OS update

    坂田 能彦, 坂田 晋也, 山口 哲平, 田宮 基裕, 鈴木 秀和, 柴木 亮太, 岡田 あすか, 横山 俊秀, 松本 啓孝, 大搗 泰一郎, 佐藤 悠城, 内田 純二, 齋藤 合, 突田 容子, 稲葉 恵, 池田 英樹, 荒井 大輔, 丸山 広高, 原 聡志, 津村 真介, 坂上 拓郎

    肺癌　64　(5)　512-512　2024/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  6. 進行非小細胞肺癌患者に対するイピリムマブ+ニボルマブ療法と放射線照射の第2相試験(NEJ053B)

    宮内 栄作, 田中 寿志, 中川 拓, 坂田 能彦, 守田 亮, 柳澤 悟, 松本 啓孝, 齋藤 良太, 田中 智, 角 俊行, 突田 容子, 前門戸 任

    肺癌　64　(5)　612-612　2024/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  7. Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial. International-journal

    Ryota Shibaki, Daichi Fujimoto, Eisaku Miyauchi, Yoko Tsukita, Ichiro Nakachi, Daisuke Arai, Yoshihiko Sakata, Naoki Shingu, Toshio Shimokawa, Takashi Kijima, Motohiro Tamiya, Sachiko Kawana, Satoshi Hara, Go Saito, Yuki Sato, Toshihide Yokoyama, Shinya Sakata, Yoshihiko Taniguchi, Akito Hata, Hirotaka Matsumoto, Teppei Yamaguchi, Nobuyuki Yamamoto

    Lung cancer (Amsterdam, Netherlands)　196　107958-107958　2024/09/19

    DOI： 10.1016/j.lungcan.2024.107958 　

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    OBJECTIVES: Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). METHODS: In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. RESULTS: Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). CONCLUSIONS: Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

  8. Risk and survival of patients with non-small cell lung cancer and pre-existing autoimmune disorders receiving immune checkpoint blockade therapy: Survival analysis with inverse probability weighting from a nationwide, multi-institutional, retrospective study (NEJ047). International-journal

    Tetsuhiko Asao, Takehito Shukuya, Kohei Uemura, Rui Kitadai, Gaku Yamamoto, Atsuto Mouri, Meiyo Tamaoka, Ryosuke Imai, Yoko Tsukita, Kazutoshi Isobe, Satoshi Watanabe, Mitsuhiro Kamimura, Ryo Morita, Keita Kudo, Minehiko Inomata, Kazunari Tateishi, Kazutaka Kakinuma, Hiroshige Yoshioka, Yukiko Namba, Issei Sumiyoshi, Taku Nakagawa, Kana Watanabe, Kunihiko Kobayashi, Kazuhisa Takahashi

    Lung cancer (Amsterdam, Netherlands)　194　107894-107894　2024/07/14

    DOI： 10.1016/j.lungcan.2024.107894 　

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    BACKGROUND: The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established. PATIENTS AND METHODS: This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan. RESULTS: In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010-February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8-37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40-21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2-57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26-0.70]; P = 0.0006). CONCLUSIONS: These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID.

  9. 当院における進行期非小細胞肺癌患者に対する院内AMOY遺伝子変異検査の検査成功率とTurn Around Timeの検討

    岩崎 史, 宮内 栄作, 井上 千裕, 青山 弥生, 小泉 照樹, 渋谷 里紗, 突田 容子, 木村 望, 伊藤 辰徳, 小野 祥直, 松本 周一郎, 成田 大輔, 遠藤 卓人, 鈴木 眞奈美, 野津田 泰嗣, 小野寺 賢, 岡田 克典

    気管支学　46　(Suppl.)　S292-S292　2024/05

    Publisher: (一社)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  10. 当院における進行期非小細胞肺癌患者に対する院内AMOY遺伝子変異検査の検査成功率とTurn Around Timeの検討

    岩崎 史, 宮内 栄作, 井上 千裕, 青山 弥生, 小泉 照樹, 渋谷 里紗, 突田 容子, 木村 望, 伊藤 辰徳, 小野 祥直, 松本 周一郎, 成田 大輔, 遠藤 卓人, 鈴木 眞奈美, 野津田 泰嗣, 小野寺 賢, 岡田 克典

    気管支学　46　(Suppl.)　S292-S292　2024/05

    Publisher: (一社)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  11. Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC. International-journal

    Nozomu Kimura, Yoko Tsukita, Risa Ebina-Shibuya, Eisaku Miyauchi, Mitsuhiro Yamada, Daisuke Narita, Ryota Saito, Chihiro Inoue, Naoya Fujino, Tomohiro Ichikawa, Tsutomu Tamada, Hisatoshi Sugiura

    Cancer biomarkers : section A of Disease markers　2024/03/20

    DOI： 10.3233/CBM-230301 　

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    BACKGROUND: Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable. OBJECTIVE: This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples. METHODS: Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines. RESULTS: Nineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P= 0.0032; median 1.2%-vs-0.3%, P= 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P= 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P= 0.0002). CONCLUSIONS: We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.

  12. 肺癌患者の血漿検体を用いたメタボローム解析による個別化医療への挑戦

    成田 大輔, 渋谷 里紗, 宮内 栄作, 突田 容子, 木村 望, 角藤 翔, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　268-268　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  13. Artemis: A Multicenter, Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of First-Line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas. International-journal

    Yusuke Okuma, Shogo Nomura, Jun Sakakibara-Konishi, Yoko Tsukita, Shuji Murakami, Yukio Hosomi, Yuichi Tambo, Yoshihito Kogure, Hiroshige Yoshioka, Motohiro Tamiya, Kiichiro Ninomiya, Eiji Iwama

    Clinical lung cancer　2024/02/08

    DOI： 10.1016/j.cllc.2024.02.002 　

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    BACKGROUND: Thymic carcinoma is a rare cancer with an aggressive clinical presentation and no organotypic symptoms. Despite using platinum-based chemotherapy as first-line treatment, the prognosis remains poor, necessitating a novel therapeutic strategy. METHODS: The artemis trial is a Phase II, single-arm, multicenter study designed to evaluate the efficacy and safety of carboplatin, paclitaxel, lenvatinib, and pembrolizumab as first-line chemotherapy for patients with advanced or recurrent thymic carcinoma. A total of 35 patients will be enrolled in this study and will receive induction therapy every 3 weeks for up to 4 cycles, followed by pembrolizumab every 3 weeks, and daily lenvatinib as maintenance therapy for up to 31 cycles (for 2 years). Lenvatinib will be continued until disease progression or unacceptable toxicity based on the discretion of the attending physician. CONCLUSION: The primary endpoint of the study is the objective response rate, with secondary endpoints including progression-free survival, overall survival, duration of response, disease control rate, and safety profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832827 Registered on April 27, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05832827. Japan Registry of Clinical Trials (jRCT), jRCT2031230114. Registered on May 22, 2023, https://jrct.niph.go.jp/latest-detail/jRCT2031230114.

  14. Corrigendum to "Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT-EP)" [Lung Cancer 186 (2023) 107426]. International-journal

    Yoshihiko Sakata, Go Saito, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Toshihide Yokoyama, Hirotaka Matsumoto, Taiichiro Otsuki, Yuki Sato, Uchida Junji, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

    Lung cancer (Amsterdam, Netherlands)　188　107450-107450　2024/02

    DOI： 10.1016/j.lungcan.2023.107450 　

  15. Durvalumab after chemoradiotherapy in non-small cell lung cancer with EGFR mutation: A real-world study (HOT2101). International-journal

    Kosuke Tsuji, Hidenori Mizugaki, Keiki Yokoo, Maki Kobayashi, Yosuke Kawashima, Nozomu Kimura, Hiroshi Yokouchi, Hajime Kikuchi, Toshiyuki Sumi, Yasutaka Kawai, Kenta Kobashi, Ryo Morita, Kenichiro Ito, Yasuo Kitamura, Hiroyuki Minemura, Keiichi Nakamura, Mari Aso, Osamu Honjo, Hisashi Tanaka, Taichi Takashina, Kyoji Tsurumi, Jun Sugisaka, Yoko Tsukita, Satoshi Konno, Satoshi Oizumi

    Cancer science　2024/01/29

    DOI： 10.1111/cas.16094 　

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    Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients.

  16. Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP)

    Yoshihiko Sakata, Go Saito, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Toshihide Yokoyama, Hirotaka Matsumoto, Taiichiro Otsuki, Yuki Sato, Uchida Junji, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

    Lung Cancer　186　107426-107426　2023/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.lungcan.2023.107426 　

    ISSN： 0169-5002

  17. 局所進行非小細胞肺癌へのPACIFICレジメン後再発に対する次治療実態調査 CRIMSON試験における探索的研究

    河内 勇人, 田宮 基裕, 大矢 由子, 松本 啓孝, 佐藤 悠城, 大搗 泰一郎, 齋藤 合, 鈴木 秀和, 福田 泰, 田中 智, 突田 容子, 内田 純二, 坂田 能彦, 中谷 有貴, 寺岡 俊輔, 荒井 大輔, 岡田 あすか, 原 聡志, 高山 浩一

    肺癌　63　(5)　489-489　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  18. 希少ドライバー遺伝子異常をもつ肺癌患者の後方視的観察研究

    荒井 大輔, 仲地 一郎, 齋藤 合, 佐藤 悠城, 突田 容子, 岡田 あすか, 松本 啓孝, 寺岡 俊輔, 田宮 基裕, 田中 智, 内田 純二, 坂田 能彦, 原 聡志, 横山 俊秀, 高岩 卓也, 河内 勇人, 谷口 善彦, 岸川 孝之

    肺癌　63　(5)　537-537　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  19. BRAF変異陽性肺癌に見られる臨床的特徴と治療効果について

    島 佑介, 仲地 一郎, 荒井 大輔, 齋藤 合, 田中 智, 横山 俊秀, 寺岡 俊輔, 内田 純二, 突田 容子, 岸川 孝之, 田宮 基裕, 河内 勇人

    肺癌　63　(5)　540-540　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  20. HER2異常を有する肺癌に見られる臨床的特徴

    田中 智, 仲地 一郎, 齋藤 合, 荒井 大輔, 田宮 基裕, 原 聡志, 内田 純二, 突田 容子, 河内 勇人, 寺岡 俊輔

    肺癌　63　(5)　660-660　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  21. 間質性肺炎合併小細胞肺癌に対するデュルバルマブ/エトポシド/カルボプラチン療法の多施設前向き介入試験

    坂田 能彦, 藤本 大智, 柴木 亮太, 仲地 一郎, 荒井 大輔, 宮内 栄作, 突田 容子, 神宮 直樹, 木島 貴志, 田宮 基裕, 川名 祥子, 原 聡志, 齋藤 合, 佐藤 悠城, 横山 俊秀, 坂田 晋也, 谷口 善彦, 秦 明登, 松本 啓孝, 山口 哲平

    肺癌　63　(5)　474-474　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  22. 非小細胞肺癌患者に対するAMOY遺伝子変異検査の院内導入における利点と今後の課題

    宮内 栄作, 井上 千裕, 青山 弥生, 小泉 照樹, 渋谷 里紗, 突田 容子, 木村 望, 成田 大輔, 野津田 泰嗣, 小野寺 賢, 岡田 克典, 杉浦 久敏

    肺癌　63　(5)　578-578　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  23. 初回治療Osimertinib多施設実態調査(OSI-FACT)の高齢者解析

    齋藤 合, 坂田 能彦, 坂田 晋也, 大矢 由子, 田宮 基裕, 鈴木 秀和, 柴木 亮太, 岡田 あすか, 横山 俊秀, 松本 啓孝, 大搗 泰一郎, 佐藤 悠城, 内田 純二, 突田 容子, 稲葉 恵, 池田 英樹, 荒井 大輔, 丸山 広高, 原 聡志, 津村 真介, 森永 潤, 坂上 拓郎

    肺癌　63　(5)　518-518　2023/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  24. A Case of IgA Vasculitis During Atezolizumab Treatment.

    Yoshinao Ono, Yoko Tsukita, Naoya Fujino, Hisatoshi Sugiura

    Internal medicine (Tokyo, Japan)　2023/08/02

    DOI： 10.2169/internalmedicine.2343-23 　

  25. 肺癌 効果予測因子 非小細胞肺癌に対する殺細胞性抗癌剤・免疫チェックポイント阻害薬併用療法の効果予測因子の探索

    木村 望, 突田 容子, 渋谷 里紗, 宮内 栄作, 角藤 翔, 成田 大輔, 斎藤 良太, 杉浦 久敏

    日本呼吸器学会誌　12　(増刊)　194-194　2023/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  26. Antibody responses to second doses of COVID-19 vaccination in lung cancer patients undergoing treatment. International-journal

    Daisuke Narita, Risa Ebina-Shibuya, Eisaku Miyauchi, Yoko Tsukita, Ryota Saito, Koji Murakami, Nozomu Kimura, Hisatoshi Sugiura

    Respiratory investigation　61　(2)　247-253　2022/12/15

    DOI： 10.1016/j.resinv.2022.11.005 　

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    BACKGROUND: Several reports have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tends to have more severe outcomes in cancer patients. Although vaccination reduces the risk of severe disease, data on antibody titers achieved by vaccination is scarce in cancer patients. METHODS: We collected 79 blood samples (69 lung cancer patients and 10 control individuals) and conducted an anti-SARS-CoV-2 antibody assay to compare the antibody titer achieved with current treatment. Sixty-eight patients (86%) received the BNT162 mRNA vaccine and 11 (14%) received the mRNA-1273 vaccine. They were categorized according to the current treatment: control individuals without cancer (cohort A), lung cancer patients who were treated with cytotoxic chemotherapy (cohort B), immunotherapy (cohort C), combination of cytotoxic chemotherapy and immunotherapy (cohort D), tyrosine kinase inhibitors (cohort E), and radiation therapy (cohort F). RESULTS: Among 69 lung cancer patients (cohort B-F), 57 (83%) had adenocarcinoma, and 66 (96%) had advanced-stage cancer. In the anti-SARS-CoV-2 antibody assay, the antibody titer was significantly lower in lung cancer patients than in control individuals (p = 0.01). The median antibody titers were 161 AU/ml in control individuals and 59.9 AU/ml in lung cancer patients. CONCLUSIONS: Antibody titers after the second vaccination were lower in cancer patients than those in healthy individuals. Our findings provide essential information for understanding the benefits and necessity of additional vaccination to prevent SARS-CoV-2 infection in lung cancer patients.

  27. Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study. International-journal

    Mihoko Imaji, Daichi Fujimoto, Yuki Sato, Yoshihiko Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Hideki Ikeda, Takashi Kijima, Hirotaka Matsumoto, Masaki Kanazu, Aoi Hino, Megumi Inaba, Yoko Tsukita, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Hiroshi Kobe, Hiromitsu Sumikawa, Shinya Sakata, Nobuyuki Yamamoto

    European journal of cancer (Oxford, England : 1990)　179　15-24　2022/11/12

    DOI： 10.1016/j.ejca.2022.10.029 　

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    INTRODUCTION: Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis. METHODS: We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge. RESULTS: In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached). CONCLUSION: Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

  28. 初回治療Osimertinibの多施設実態調査(OSI-FACT)の追跡調査報告

    大矢 由子, 坂田 能彦, 坂田 晋也, 田宮 基裕, 鈴木 秀和, 柴木 亮太, 岡田 あすか, 神戸 寛史, 松本 啓孝, 大搗 泰一郎, 佐藤 悠城, 金津 正樹, 齋藤 合, 突田 容子, 稲葉 恵, 池田 英樹, 荒井 大輔, 丸山 広高, 森永 潤, 坂上 拓郎

    肺癌　62　(6)　658-658　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  29. Uncommon EGFR mutationに対する初回オシメルチニブの有効性・安全性に関する検討

    突田 容子, 坂田 能彦, 田宮 基裕, 柴木 亮太, 大矢 由子, 金津 正樹, 稲葉 恵, 坂田 晋也, 鈴木 秀和, 神戸 寛史, 日野 葵, 池田 英樹, 丸山 広高, 坂上 拓郎

    肺癌　62　(6)　689-689　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  30. Durvalumab承認後,化学放射線治療を受けた局所進行NSCLCにおける予後予測因子の検討(CRIMSON試験)

    大矢 由子, 河内 勇人, 谷口 善彦, 松本 啓孝, 佐藤 悠城, 大搗 泰一郎, 斎藤 合, 鈴木 秀和, 福田 泰, 田中 智, 突田 容子, 金津 正樹, 坂田 能彦, 中谷 有貴, 寺岡 俊輔, 荒井 大輔, 岡田 あすか, 原 聡志

    肺癌　62　(6)　583-583　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  31. 初回治療Osimertinibの実臨床実態調査(OSI-FACT)におけるPS不良例の解析

    田宮 基裕, 坂田 能彦, 池田 英樹, 齋藤 合, 鈴木 秀和, 原 聡志, 突田 容子, 木島 貴志, 松本 啓孝, 佐藤 悠城, 金津 正樹, 丸山 広高, 稲葉 恵, 荒井 大輔, 津村 伸介, 大矢 由子, 神戸 寛史, 岡田 あすか, 坂田 晋也, 藤本 大智

    肺癌　62　(6)　634-634　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  32. 初回治療Osimertinibの多施設実態調査(OSI-FACT)の追跡調査報告

    大矢 由子, 坂田 能彦, 坂田 晋也, 田宮 基裕, 鈴木 秀和, 柴木 亮太, 岡田 あすか, 神戸 寛史, 松本 啓孝, 大搗 泰一郎, 佐藤 悠城, 金津 正樹, 齋藤 合, 突田 容子, 稲葉 恵, 池田 英樹, 荒井 大輔, 丸山 広高, 森永 潤, 坂上 拓郎

    肺癌　62　(6)　658-658　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  33. EGFR陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査に付随する薬剤性肺障害の検討

    佐藤 悠城, 澄川 裕充, 柴木 亮太, 森本 剛, 坂田 能彦, 大矢 由子, 田宮 基裕, 鈴木 秀和, 松本 啓孝, 木島 貴志, 橋本 和樹, 神戸 寛史, 日野 葵, 稲葉 恵, 突田 容子, 池田 英樹, 荒井 大輔, 丸山 広高, 原 聡志, 津村 真介, 坂田 晋也, 藤本 大智

    肺癌　62　(6)　658-658　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  34. 初回治療オシメルチニブによる薬剤性肺障害発症後リチャレンジの安全性,有効性に関する検討

    今地 美帆子, 藤本 大智, 佐藤 悠城, 坂田 能彦, 大矢 由子, 田宮 基裕, 鈴木 秀和, 池田 英樹, 木島 貴志, 松本 啓孝, 金津 正樹, 齋藤 合, 稲葉 恵, 突田 容子, 荒井 大輔, 丸山 広高, 原 聡志, 津村 真介, 神戸 寛史, 坂田 晋也

    肺癌　62　(6)　658-658　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  35. Uncommon EGFR mutationに対する初回オシメルチニブの有効性・安全性に関する検討

    突田 容子, 坂田 能彦, 田宮 基裕, 柴木 亮太, 大矢 由子, 金津 正樹, 稲葉 恵, 坂田 晋也, 鈴木 秀和, 神戸 寛史, 日野 葵, 池田 英樹, 丸山 広高, 坂上 拓郎

    肺癌　62　(6)　689-689　2022/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  36. The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. International-journal

    Yuichiro Takeda, Yusaku Kusaba, Yoko Tsukita, Yukari Uemura, Eisaku Miyauchi, Takaya Yamamoto, Hiroshi Mayahara, Akito Hata, Hidetsugu Nakayama, Satoshi Tanaka, Junji Uchida, Kazuhiro Usui, Tatsuya Toyoda, Motohiro Tamiya, Masahiro Morimoto, Yuko Oya, Takeshi Kodaira, Keiichi Jingu, Hisatoshi Sugiura

    Clinical and translational radiation oncology　37　57-63　2022/11

    DOI： 10.1016/j.ctro.2022.08.010 　

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    Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

  37. Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy

    Koji Murakami, Hirohito Sano, Naoki Tode, Yoko Tsukita, Kei Sato, Daisuke Narita, Nozomu Kimura, Shuichiro Matsumoto, Yoshinao Ono, Chikashi Iwasaki, Hatsumi Sugiyama, Manami Suzuki, Sho Kakuto, Shuichi Konno, Hajime Kanamori, Hiroaki Baba, Kengo Oshima, Kentarou Takei, Koichi Tokuda, Tsutomu Tamada, Hisatoshi Sugiura

    BMJ OPEN RESPIRATORY RESEARCH　9　(1)　2022/09

    DOI： 10.1136/bmjresp-2022-001332 　

    eISSN： 2052-4439

  38. Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study

    Takaya Yamamoto, Yu Katagiri, Yoko Tsukita, Haruo Matsushita, Rei Umezawa, Yoshiyuki Katsuta, Noriyuki Kadoya, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Keita Kishida, So Omata, Eisaku Miyauchi, Ryota Saito, Keiichi Jingu

    Cancers　14　(16)　3993-3993　2022/08/18

    Publisher: MDPI AG

    DOI： 10.3390/cancers14163993 　

    eISSN： 2072-6694

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    Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. Materials and Methods: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1–5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. Results: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3–22.2%), 20.1% (95% CI: 6.0–40.2%), 59.2% (95% CI: 34.4–77.3%), and 78.2% (95% CI: 51.4–91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. Conclusions: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.

  39. Decreased expression of airway epithelial Axl is associated with eosinophilic inflammation in severe asthma. International-journal

    Koji Itakura, Naoya Fujino, Yosuke Kamide, Ikuo Saito, Mitsuhiro Yamada, Koji Okutomo, Yoko Tsukita, Takuya Saito, Tomohiro Ichikawa, Tadahisa Numakura, Yorihiko Kyogoku, Hiroyuki Aizawa, Yoshinao Ono, Shuichiro Matsumoto, Tracy Hussell, Masami Taniguchi, Masakazu Ichinose, Hisatoshi Sugiura

    Allergology international : official journal of the Japanese Society of Allergology　71　(3)　383-394　2022/07

    DOI： 10.1016/j.alit.2022.02.010 　

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    BACKGROUND: Airway epithelium-derived cytokines are critical to provoke and perpetuate type 2 inflammation in asthma. Yet it is poorly understood how this epithelial cell-driven inflammatory response is negatively regulated. We previously reported that Axl receptor tyrosine kinase was expressed by basal cells in the airway epithelium and had a role in defining their stem cell identity. However, whether and how Axl regulates airway type 2 inflammation remains unknown. METHODS: We performed immunofluorescence staining to compare Axl expression in airway epithelium between non-asthmatic subjects, mild-moderate asthma and severe asthma. We confirmed this result by interrogating public databases of global gene expression in endobronchial biopsies. We then quantified eosinophil numbers infiltrating into the trachea of wild-type or Axl-knockout mice that were intranasally treated with house dust mite extracts (HDM). Cell-based assays using siRNA targeting Axl were further performed to identify molecules involved in Axl-mediated regulation of inflammation. RESULTS: Histological assessments and transcriptome analyses revealed decreases in protein and mRNA of Axl in airway basal cells of severe asthmatics. This reduction of Axl expression was correlated with infiltration of eosinophils and mast cells in severe asthmatics. Eosinophil infiltration was more evident in the trachea of Axl-knockout mice in response to repetitive HDM administration. siRNA-mediated knockdown of Axl increased mRNA and protein expression of granulocyte macrophage-colony stimulating factor (GM-CSF) in human bronchial epithelial cells. CONCLUSIONS: Axl kinase expressed by basal cells may suppress excessive eosinophilic inflammation via inhibition of GM-CSF in the airway. Axl reduction has clinical implications for the pathogenesis of severe asthma.

  40. Drug-related pneumonitis induced by osimertinib as first-line treatment for EGFR-positive non-small cell lung cancer: a real-world setting. International-journal

    Yuki Sato, Hiromitsu Sumikawa, Ryota Shibaki, Takeshi Morimoto, Yoshihiko Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Hirotaka Matsumoto, Takashi Yokoi, Kazuki Hashimoto, Hiroshi Kobe, Aoi Hino, Megumi Inaba, Yoko Tsukita, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Shinya Sakata, Daichi Fujimoto

    Chest　162　(5)　1188-1198　2022/06/01

    DOI： 10.1016/j.chest.2022.05.035 　

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    BACKGROUND: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data are currently lacking. RESEARCH QUESTION: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest computed tomography (CT) scans and clinical information during osimertinib exposure were collected until June 2020. The primary endpoint was DRP incidence identified through central review. RESULTS: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) were diagnosed with DRP (all grades), and 21 patients (4.6%) had ≥grade 3 DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and non-specific interstitial pneumonia were found in 30, 21, 18, 9, and 2 patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio: 1.72, 95% confidence interval: 1.01-2.89, P=0.046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not negatively affect treatment efficacy. INTERPRETATION: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.

  41. Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. International-journal

    Takaya Yamamoto, Yoko Tsukita, Yu Katagiri, Haruo Matsushita, Rei Umezawa, Yojiro Ishikawa, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Eisaku Miyauchi, Ryota Saito, Yoshiyuki Katsuta, Noriyuki Kadoya, Keiichi Jingu

    BMC cancer　22　(1)　364-364　2022/04/04

    DOI： 10.1186/s12885-022-09354-1 　

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    BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

  42. 修飾核酸一斉定量系を用いたCOPD・肺がん鑑別手法の検討

    渡辺 匠, 平本 航大, 沼倉 忠久, 宮内 栄作, 突田 容子, 杉浦 久敏, 松本 洋太郎, 富岡 佳久

    日本薬学会年会要旨集　142年会　26M-pm08S　2022/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  43. 修飾核酸一斉定量系を用いたCOPD・肺がん鑑別手法の検討

    渡辺 匠, 平本 航大, 沼倉 忠久, 宮内 栄作, 突田 容子, 杉浦 久敏, 松本 洋太郎, 富岡 佳久

    日本薬学会年会要旨集　142年会　26M-pm08S　2022/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  44. Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer. International-journal

    Takaya Yamamoto, Yoshiyuki Katsuta, Kiyokazu Sato, Yoko Tsukita, Rei Umezawa, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Keita Kishida, So Omata, Eisaku Miyauchi, Ryota Saito, Noriyuki Kadoya, Keiichi Jingu

    PloS one　17　(12)　e0278707　2022

    DOI： 10.1371/journal.pone.0278707 　

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    BACKGROUND AND PURPOSE: The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy. MATERIALS AND METHODS: Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r). RESULTS: Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively). CONCLUSIONS: The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.

  45. リンパ行性転移が示唆された小細胞肺癌術後気管内再発の1例

    木村 望, 突田 容子, 宮内 栄作, 小室 英恵, 齊藤 涼子, 佐藤 輝幸, 宍倉 裕, 野津田 泰嗣, 桜田 晃, 杉浦 久敏

    気管支学　44　(1)　69-72　2022/01

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  46. リンパ行性転移が示唆された小細胞肺癌術後気管内再発の1例

    木村 望, 突田 容子, 宮内 栄作, 小室 英恵, 齊藤 涼子, 佐藤 輝幸, 宍倉 裕, 野津田 泰嗣, 桜田 晃, 杉浦 久敏

    気管支学　44　(1)　69-72　2022/01

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  47. Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT). International-journal

    Yoshihiko Sakata, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Hiroshi Kobe, Hirotaka Matsumoto, Takashi Yokoi, Yuki Sato, Takeshi Uenami, Go Saito, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

    European journal of cancer (Oxford, England : 1990)　159　144-153　2021/12

    DOI： 10.1016/j.ejca.2021.09.041 　

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    BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.

  48. 切除不能III期非小細胞肺癌に対する強度変調放射線治療を用いた化学放射線療法に関しての後方視的研究

    草場 勇作, 竹田 雄一郎, 突田 容子, 山本 貴也, 宮内 栄作, 馬屋原 博, 秦 明登, 田中 智, 内田 純二, 臼井 一裕, 田宮 基裕, 大矢 由子

    肺癌　61　(6)　592-592　2021/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  49. Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study. International-journal

    Yoko Tsukita, Takaya Yamamoto, Hiroshi Mayahara, Akito Hata, Yuichiro Takeda, Hidetsugu Nakayama, Satoshi Tanaka, Junji Uchida, Kazuhiro Usui, Tatsuya Toyoda, Motohiro Tamiya, Masahiro Morimoto, Yuko Oya, Takeshi Kodaira, Eisaku Miyauchi, Keiichi Jingu, Hisatoshi Sugiura

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology　160　266-272　2021/05/21

    DOI： 10.1016/j.radonc.2021.05.016 　

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    BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. MATERIALS AND METHODS: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. RESULTS: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. CONCLUSION: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.

  50. 当院におけるIMRTによる根治的放射線化学療法後のデュルバルマブ投与症例の検討

    木村 望, 突田 容子, 斎藤 良太, 佐藤 輝幸, 宮内 栄作, 井上 彰, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　139-139　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  51. ALK-IHC陽性肺腺癌に対してアレクチニブを投与したが奏効せず、後にROS1陽性が判明しクリゾチニブが奏効した1例

    杉山 初美, 宮内 栄作, 齋藤 勉, 相澤 洋之, 突田 容子, 齋藤 良太, 佐藤 輝幸, 宍倉 裕, 杉浦 久敏, 齊藤 涼子

    肺癌　60　(7)　1032-1032　2020/12

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  52. ALK-IHC陽性肺腺癌に対してアレクチニブを投与したが奏効せず、後にROS1陽性が判明しクリゾチニブが奏効した1例

    杉山 初美, 宮内 栄作, 齋藤 勉, 相澤 洋之, 突田 容子, 齋藤 良太, 佐藤 輝幸, 宍倉 裕, 杉浦 久敏, 齊藤 涼子

    肺癌　60　(7)　1032-1032　2020/12

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  53. Immunotherapy-related hepatitis and thrombocytopaenia induced by the very low dose of only 90 mg of atezolizumab. International-journal

    Yoko Tsukita, Eisaku Miyauchi, Masahide Fukudo, Takaaki Sasaki, Masakazu Ichinose

    European journal of cancer (Oxford, England : 1990)　133　22-24　2020/07

    DOI： 10.1016/j.ejca.2020.04.008 　

  54. Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study. International-journal

    Kazunari Tateishi, Ryo Ko, Takehito Shukuya, Yusuke Okuma, Satoshi Watanabe, Shoichi Kuyama, Kyoko Murase, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Mouri, Takao Miyabayashi, Hiroyuki Sakashita, Yoko Matsumoto, Tomoyuki Tanigawa, Tomonobu Koizumi, Satoshi Morita, Kunihiko Kobayashi, Toshihiro Nukiwa, Kazuhisa Takahashi

    The oncologist　25　(4)　e668-e674　2020/04

    DOI： 10.1634/theoncologist.2019-0593 　

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    BACKGROUND: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. MATERIAL AND METHODS: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second-line chemotherapy were obtained from medical records. RESULTS: In total, 191 patients were enrolled in this study. Second-line chemotherapy included platinum-based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow-up time was 50.5 months, and the median overall survival (OS) from the start of second-line chemotherapy was 22.4 (95% confidence interval, 17.5-26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum-based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum-based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). CONCLUSION: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second-line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. IMPLICATIONS FOR PRACTICE: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second-line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.

  55. A case of localized tracheobronchial relapsing polychondritis with positive matrilin-1 staining. International-journal Peer-reviewed

    Tomonori Makiguchi, Akira Koarai, Chihiro Inoue, Yayoi Aoyama, Taizo Hirano, Takashi Ohe, Tomohiro Ichikawa, Yutaka Shishikura, Hanae Komuro, Yoko Tsukita, Naoki Tode, Tadahisa Numakura, Tsutomu Saito, Teruyuki Sato, Yoshiya Mitsuhashi, Tsutomu Tamada, Hisatoshi Sugiura, Masakazu Ichinose

    BMC rheumatology　4　1-1　2020

    DOI： 10.1186/s41927-019-0103-6 　

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    Background: Relapsing polychondritis (RPC) is a rare progressive autoimmune disease characterized by inflammation in the cartilage of multiple organs. Tracheobronchial involvement appears in nearly half of RPC patients during the course of their disease and represents the main cause of death. Localized tracheobronchial RPC is much rarer, and the pathogenesis remains unclear. Matrilin-1 is a non-collagenous cartilage matrix protein and has been suggested to be a potent autoantigen that induces the airway disease of RPC in animal models. However, the expression of matrilin-1 in tracheobronchial tissue in human remains unclear. Therefore, we examined the expression of matrilin-1 in the tracheal and auricular tissues in a localized tracheobronchial RPC patient. Case presentation: A 62-year-old man with systemic sclerosis presented with cough and dyspnea on exertion. The lung function test showed an expiratory flow limitation and chest computed tomography showed diffuse thickness from the trachea to the bronchiole. No other tests showed abnormal findings. To evaluate further, bronchoscopy was performed and endobronchial ultrasonography showed thickness in the fourth-marginal echo layer suggesting inflammation of the cartilage. However, the tracheal biopsy showed no specific findings. The subsequent surgical tracheal biopsies showed inflammatory cell infiltration with destruction of the cartilage. Neither auricular nor nasal deformity, except for a tracheobronchial lesion, was detected. Biopsy from the left auricular cartilage also did not show any inflammatory changes. Finally, we diagnosed the patient with localized tracheobronchial RPC. To address the hypothesis that autoimmunity against matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC, we evaluated the expression level of matrilin-1 in a tracheal and auricular specimen from this patient. Immunohistochemical staining with anti-matrilin-1 antibody showed matrilin-1 in the tracheal but not in the auricular cartilage. Conclusions: We first demonstrated the expression of matrilin-1 in tracheal but not in auricular cartilage in a localized tracheobronchial RPC patient. This result supports the possibility that matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC. However, this is only one case report and further observations will be needed to confirm this result.

  56. 強度変調放射線治療による根治的化学放射線療法後のデュルバルマブ使用経験の報告

    突田 容子, 宮内 栄作, 斎藤 良太, 佐藤 輝幸, 山本 貴也, 片桐 佑, 井上 彰, 一ノ瀬 正和

    肺癌　59　(6)　674-674　2019/11

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  57. Phase II study of S-1 in patients with previously-treated invasive thymoma and thymic carcinoma: North Japan lung cancer study group trial 1203. Peer-reviewed

    Tsukita Y, Inoue A, Sugawara S, Kuyama S, Nakagawa T, Harada D, Tanaka H, Watanabe K, Mori Y, Harada T, Hino T, Fujii M, Ichinose M

    Lung Cancer　18　(139)　89-93　2019/10

  58. 免疫療法の効果と耐性 EGFR遺伝子変異陽性/陰性肺癌におけるT細胞受容体レパトア解析(Cancer immunotherapy sensitivity and resistance TCR repertoires in lung adenocarcinomas with and without EGFR mutation)

    宮内 栄作, 松田 達雄, 清谷 一馬, Low Siew-Kee, 突田 容子, 一ノ瀬 正和, 桜田 晃, 岡田 克典, 齊藤 涼子, 中村 祐輔

    日本癌学会総会記事　78回　S19-1　2019/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  59. Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations International-journal Peer-reviewed

    Miyauchi E, Matsuda T, Kiyotani K, Low SK, Hsu YW, Tsukita Y, Ichinose M, Sakurada A, Okada Y, Saito R, Nakamura Y

    Cancer Science　110　(3)　867-874　2019/03

    DOI： 10.1111/cas.13919 　

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    Recent clinical trials of non-small cell lung cancer with immune checkpoint inhibitors revealed that patients with epidermal growth factor receptor (EGFR) mutations had more unfavorable outcomes compared with those with wild-type EGFR. However, the underlying mechanism for the link between EGFR mutations and immune resistance remains unclear. We performed T cell receptor (TCR) repertoire analysis of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate the characteristics of TCR repertoires. We collected a total of 39 paired (normal and tumor) lung tissue samples (20 had EGFR mutations) and conducted TCR repertoire analysis as well as whole-exome sequencing (WES) and transcriptome analysis. The TCR diversity index in EGFR-mutant tumors was significantly higher than that in EGFR-wild-type tumors (median [range] 552 [162-1,135] vs 230 [30-764]; P < .01), suggesting higher T cell clonal expansion in EGFR-wild-type tumors than in EGFR-mutant tumors. In WES, EGFR-mutant tumors showed lower numbers of non-synonymous mutations and predicted neoantigens than EGFR-wild-type tumors (P < .01, P = .03, respectively). The number of non-synonymous mutations revealed a positive correlation with the sum of frequencies of the TCRβ clonotypes of 1% or higher in tumors (r = .52, P = .04). The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR-mutant and wild-type lung tumors. Our findings provide important information for understanding the molecular mechanism behind EGFR-mutant patients showing unfavorable responses to immune checkpoint inhibitors.

  60. Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas Peer-reviewed

    Yoko Tsukita, Naoya Fujino, Eisaku Miyauchi, Ryoko Saito, Fumiyoshi Fujishima, Koji Itakura, Yorihiko Kyogoku, Koji Okutomo, Mitsuhiro Yamada, Tatsuma Okazaki, Hisatoshi Sugiura, Akira Inoue, Yoshinori Okada, Masakazu Ichinose

    Molecular Cancer　18　(1)　24　2019/02/11

    DOI： 10.1186/s12943-019-0953-y 　

    eISSN： 1476-4598

  61. Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5. International-journal Peer-reviewed

    Yoko Tsukita, Tatsuma Okazaki, Satoru Ebihara, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Taizou Hirano, Hisatoshi Sugiura, Tsutomu Tamada, Nobuyuki Tanaka, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose

    Oncoimmunology　8　(2)　e1543526　2019

    DOI： 10.1080/2162402X.2018.1543526 　

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    Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.

  62. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を促進する(Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas)

    突田 容子, 宮内 栄作, 齊藤 涼子, 岡崎 達馬, 井上 彰, 岡田 克典, 一ノ瀬 正和

    日本癌学会総会記事　77回　1885-1885　2018/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  63. EGFR遺伝子変異陽性肺腺癌におけるT細胞受容体レパトア解析(T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations)

    宮内 栄作, 松田 達雄, Hsu Yu-Wen, 突田 容子, 一ノ瀬 正和, 桜田 晃, 岡田 克典, 齊藤 涼子, 清谷 一馬, 中村 祐輔

    日本癌学会総会記事　77回　2036-2036　2018/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  64. Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems. International-journal Peer-reviewed

    Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose

    Journal of cachexia, sarcopenia and muscle　9　(4)　643-653　2018/08

    DOI： 10.1002/jcsm.12297 　

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    BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. METHODS: We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. RESULTS: The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. CONCLUSIONS: Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis-swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.

  65. ARDSを合併したChlamydophila pneumoniae感染症の1例

    突田容子, 山田充啓, 大江崇, 伊藤俊輔, 小林誠, 玉井ときわ, 小荒井晃, 玉田勉, 杉浦久敏, 一ノ瀬正和

    日本内科学会雑誌　105　(12)　2426-2431　2016/12

    Publisher:

    DOI： 10.2169/naika.105.2426 　

    ISSN： 0021-5384

    eISSN： 1883-2083

  66. EGFR Mutation Analysis of Circulating Tumor DNA Using an Improved PNA-LNA PCR Clamp Method Peer-reviewed

    Kana Watanabe, Tatsuro Fukuhara, Yoko Tsukita, Mami Morita, Aya Suzuki, Nobuyuki Tanaka, Hiroshi Terasaki, Toshihiro Nukiwa, Makoto Maemondo

    CANADIAN RESPIRATORY JOURNAL　5297329　2016

    DOI： 10.1155/2016/5297329 　

    ISSN： 1198-2241

    eISSN： 1916-7245

  67. Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma Peer-reviewed

    Yoko Tsukita, Tatsuro Fukuhara, Maki Kobayashi, Mami Morita, Aya Suzuki, Kana Watanabe, Tetsuya Noguchi, Yasuko Kurata, Manabu Suno, Makoto Maemondo

    INTERNAL MEDICINE　54　(24)　3185-3188　2015

    DOI： 10.2169/internalmedicine.54.4996 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  68. ベバシズマブとエルロチニブの併用療法中に腸管気腫症を発症した肺腺癌の1例 Peer-reviewed

    突田容子, 渡邉香奈, 盛田麻美, 綿貫善太, 鈴木綾, 福原達朗, 内海潔, 藤谷恒明, 前門戸任

    日本呼吸器学会誌　3　(3)　442-445　2014/05

    Publisher:

    ISSN： 2186-5876

  69. Large-cell neuroendocrine carcinoma with epidermal growth factor receptor mutation: Possible transformation of lung adenocarcinoma Peer-reviewed

    Satoru Yanagisawa, Naoto Morikawa, Yuichiro Kimura, Yoko Nagano, Kazuhiro Murakami, Toshiharu Tabata

    RESPIROLOGY　17　(8)　1275-1277　2012/11

    DOI： 10.1111/j.1440-1843.2012.02258.x 　

    ISSN： 1323-7799

    eISSN： 1440-1843

Show all ︎Show first 5

Misc. 41

  1. 修飾核酸一斉定量系を用いたCOPD早期発見手法の開発検討

    渡辺匠, 平本航大, 沼倉忠久, 滝田克也, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

    日本薬学会東北支部大会講演要旨集　59th　2020

  2. TCR repertoires in lung adenocarcinomas with and without EGFR mutation

    宮内栄作, 松田達雄, 清谷一馬, LOW Siew-kee, 突田容子, 一ノ瀬正和, 桜田晃, 岡田克典, 齊藤涼子, 中村祐輔

    日本癌学会学術総会抄録集(Web)　78th　2019

  3. 胸腔鏡下肺切除術で診断された印環細胞癌様の形態を呈した肺腺癌の1例

    宮内栄作, 成田大輔, 相澤洋之, 村上康司, 小林誠, 突田容子, 東出直樹, 齋藤良太, 佐藤輝幸, 杉浦久敏, 一ノ瀬正和, 齊藤涼子, 松田安史, 岡田克典

    肺癌(Web)　59　(5)　2019

    ISSN： 1348-9992

  4. T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations

    Eisaku Miyauchi, Tatsuo Matsuda, Yu-wen Hsu, Yoko Tsukita, Masakazu Ichinose, Akira Sakurada, Yoshinori Okada, Ryoko Saito, Kazuma Kiyotani, Yusuke Nakamura

    CANCER SCIENCE　109　1178-1178　2018/12

    ISSN： 1349-7006

  5. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を促進する(Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas)

    突田 容子, 宮内 栄作, 齊藤 涼子, 岡崎 達馬, 井上 彰, 岡田 克典, 一ノ瀬 正和

    日本癌学会総会記事　77回　1885-1885　2018/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  6. EGFR遺伝子変異陽性肺腺癌におけるT細胞受容体レパトア解析(T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations)

    宮内 栄作, 松田 達雄, Hsu Yu-Wen, 突田 容子, 一ノ瀬 正和, 桜田 晃, 岡田 克典, 齊藤 涼子, 清谷 一馬, 中村 祐輔

    日本癌学会総会記事　77回　2036-2036　2018/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  7. リンパ管を標的とした新規胸膜炎治療の検討

    小林誠, 岡崎達馬, 突田容子, 小松理世, 杉浦久敏, 海老原覚, 一ノ瀬正和

    日本呼吸器学会誌(Web)　7　209　2018/03/10

    ISSN： 2186-5884

  8. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田容子, 藤野直也, 宮内栄作, 井上彰, 板倉康司, 山田充啓, 岡崎達馬, 桜田晃, 杉浦久敏, 岡田克典, 一ノ瀬正和

    日本呼吸器学会誌(Web)　7　267　2018/03/10

    ISSN： 2186-5884

  9. リンパ管を標的とした新規胸膜炎治療の検討

    小林 誠, 岡崎 達馬, 突田 容子, 小松 理世, 杉浦 久敏, 海老原 覚, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　209-209　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  10. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田 容子, 藤野 直也, 宮内 栄作, 井上 彰, 板倉 康司, 山田 充啓, 岡崎 達馬, 桜田 晃, 杉浦 久敏, 岡田 克典, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　267-267　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  11. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田 容子, 藤野 直也, 宮内 栄作, 井上 彰, 板倉 康司, 山田 充啓, 岡崎 達馬, 桜田 晃, 杉浦 久敏, 岡田 克典, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　267-267　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  12. 高齢者の誤嚥・肺炎予防up‐to‐date 6.サルコペニアと誤嚥性肺炎の関係

    岡崎達馬, 小松理世, 突田容子, 小林誠, 二瓶真由美, 海老原孝枝, 一ノ瀬正和

    Geriatric Medicine　55　(11)　1221‐1224-1224　2017/11/01

    Publisher: (株)ライフ・サイエンス

    ISSN： 0387-1088

  13. スニチニブは腫瘍の微小環境を改善してエフェクターT細胞を浸潤させDR-5を介した抗腫瘍免疫療法の効果を増強する

    突田 容子, 岡崎 達馬, 佐藤 靖史, 八木田 秀雄, 一ノ瀬 正和

    日本癌学会総会記事　76回　E-1057　2017/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  14. Effects of a combination of antiangiogenic and antilymphangiogenic therapies on a death receptor-5 mediated antitumor immunotherapy in mice. Peer-reviewed

    Yoko Tsukita, Tatsuma Okazaki, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose

    JOURNAL OF CLINICAL ONCOLOGY　35　2017/05

    DOI： 10.1200/JCO.2017.35.15_suppl.e23001 　

    ISSN： 0732-183X

    eISSN： 1527-7755

  15. サルコイドーシス診断に有用な因子の検討

    光根歩, 佐藤輝幸, 柳澤悟, 突田容子, 東條裕, 小野学, 宮内栄作, 一ノ瀬正和

    気管支学　39　(Suppl.)　S274-S274　2017/05/01

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  16. Mycobacterium shinjukuense肺感染症の1例

    山田充啓, 玉井ときわ, 突田容子, 玉田勉, 杉浦久敏, 一ノ瀬正和, 鹿住祐子

    結核　92　(5)　448-448　2017/05

    Publisher: (一社)日本結核病学会

    ISSN： 0022-9776

    eISSN： 1884-2410

  17. 誤嚥性肺炎の新規治療標的としてのリンパ管と筋肉:サルコペニアを含めた実験モデルと症例の解析

    岡崎達馬, 小松理世, 小林誠, 突田容子, 二瓶真由美, 海老原覚, 海老原孝枝, 一ノ瀬正和

    日本老年医学会雑誌　54　(Suppl.)　110-110　2017/05

    Publisher: (一社)日本老年医学会

    ISSN： 0300-9173

  18. 誤嚥性肺炎はマイオカインを誘導しサルコペニアを悪化させる

    小松理世, 岡崎達馬, 突田容子, 小林誠, 二瓶真由美, 杉浦久敏, 海老原孝枝, 海老原覚, 一ノ瀬正和

    日本老年医学会雑誌　54　(Suppl.)　149-149　2017/05

    Publisher: (一社)日本老年医学会

    ISSN： 0300-9173

  19. 誤嚥性肺炎はマイオカインを誘導し筋肉を萎縮させる

    小松理世, 岡崎達馬, 突田容子, 小林誠, 二瓶真由美, 杉浦久敏, 海老原覚, 一ノ瀬正和

    日本呼吸器学会誌(Web)　6　116　2017/03/10

    ISSN： 2186-5884

  20. 誤嚥性肺炎はマイオカインを誘導し筋肉を萎縮させる

    小松 理世, 岡崎 達馬, 突田 容子, 小林 誠, 二瓶 真由美, 杉浦 久敏, 海老原 覚, 一ノ瀬 正和

    日本呼吸器学会誌　6　(増刊)　116-116　2017/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  21. Case Report : A case of infection of Chlamydophila pneumoniae with ARDS

    突田 容子, 山田 充啓, 大江 崇, 伊藤 俊輔, 小林 誠, 玉井 ときわ, 小荒井 晃, 玉田 勉, 杉浦 久敏, 一ノ瀬 正和

    日本内科学会雑誌　105　(12)　2426-2431　2016/12/10

    Publisher: 日本内科学会

    ISSN： 0021-5384

  22. EBUS-TBNAで診断に至った肺原発血管肉腫の1例

    京極 自彦, 岡崎 達馬, 三浦 絵美里, 突田 容子, 田中 里江, 東條 裕, 三橋 善哉, 宮内 栄作, 杉浦 久敏, 一ノ瀬 正和, 高橋 信

    肺癌　56　(5)　406-406　2016/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  23. 気管支鏡検査で菌検出が可能であった好酸球増多を伴う肺接合菌症の1例

    突田 容子, 平野 泰三, 佐藤 慶, 高橋 秀徳, 村上 康司, 玉井 ときわ, 山田 充啓, 玉田 勉, 杉浦 久敏, 一ノ瀬 正和

    肺癌　56　(5)　405-405　2016/10

    Publisher: (NPO)日本肺癌学会

    ISSN： 0386-9628

    eISSN： 1348-9992

  24. 抗血管新生と抗リンパ管新生療法の組み合わせは抗腫瘍免疫療法の効果を増強する

    突田 容子, 岡崎 達馬, 八木田 秀雄, 一ノ瀬 正和

    日本癌学会総会記事　75回　P-2126　2016/10

    ISSN： 0546-0476

  25. EBUS‐TBNAで診断に至った肺原発血管肉腫の1例

    京極自彦, 岡崎達馬, 三浦絵美里, 突田容子, 田中里江, 東條裕, 三橋善哉, 宮内栄作, 杉浦久敏, 一ノ瀬正和, 高橋信

    気管支学　38　(5)　445‐446-446　2016/09/25

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  26. 気管支鏡検査で菌検出が可能であった好酸球増多を伴う肺接合菌症の1例

    突田容子, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 山田充啓, 玉田勉, 杉浦久敏, 一ノ瀬正和

    気管支学　38　(5)　445-445　2016/09

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  27. Second-line chemotherapy efficacy in patients with previously treated advanced thymic carcinoma: A retrospective analysis of 192 patients from NEJ023 Study.

    Shunichiro Iwasawa, Ryo Ko, Takehito Shukuya, Satoshi Watanabe, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Ryo Ito, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Moun, Takao Miyabayashi, Hiroyuki Sakashita, Yoko Matsumoto, Tomoyuki Tanigawa, Satoshi Morita, Kazuhisa Takahashi

    JOURNAL OF CLINICAL ONCOLOGY　34　(15)　2016/05

    DOI： 10.1200/JCO.2016.34.15_suppl.8569 　

    ISSN： 0732-183X

    eISSN： 1527-7755

  28. 誤嚥性肺炎はマイオカイン及び筋萎縮を誘導する~動物モデルを用いた解析~

    岡崎達馬, 小松理世, 小林誠, 二瓶真由美, 突田容子, 海老原覚, 一ノ瀬正和

    日本老年医学会雑誌　53　(Suppl.)　143-143　2016/05

    Publisher: (一社)日本老年医学会

    ISSN： 0300-9173

  29. 正常及び敗血症モデルマウスの胸膜(横隔膜)のリンパ管の解析

    小林誠, 岡崎達馬, 二瓶真由美, 突田容子, 小松理世, 玉井ときわ, 杉浦久敏, 一ノ瀬正和

    日本呼吸器学会誌　5　(増刊)　304-304　2016/03/10

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  30. 誤嚥性肺炎は呼吸筋,骨格筋,嚥下筋の萎縮を誘導する

    小松理世, 岡崎達馬, 二瓶真由美, 小林誠, 突田容子, 杉浦久敏, 海老原覚, 一ノ瀬正和

    日本呼吸器学会誌　5　(増刊)　175-175　2016/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  31. alectinib耐性後にc‐Met遺伝子増幅を来しcrizotinibが奏効したALK融合遺伝子陽性肺腺癌の一例

    渡辺香奈, 突田容子, 盛田麻美, 鈴木綾, 福原達朗, 玉井恵一, 片山量平, 前門戸任

    日本肺癌学会総会号　56th　658　2015/10/05

    ISSN： 0386-9628

  32. ガイドシース併用気管支腔内超音波断層法(EBUS‐GS)における擦過回数と診断率の検討

    突田容子, 渡邉香奈, 佐藤ひかり, 盛田麻美, 鈴木綾, 福原達朗, 伊藤しげみ, 佐藤郁郎, 前門戸任

    気管支学　37　S171　2015/05/01

    Publisher: 特定非営利活動法人 日本呼吸器内視鏡学会

    DOI： 10.18907/jjsre.37.Special_S171_2 　

    ISSN： 0287-2137

  33. 高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定

    渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 寺崎浩司, 前門戸任

    日本呼吸器学会誌　4　131　2015/03/10

    ISSN： 2186-5876

  34. 高感度改良型PNA‐LNAクランプ法を用いた非小細胞肺癌血漿中循環DNAのEGFR遺伝子変異測定によるEGFR‐TKI効果予測

    渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 田中伸幸, 寺崎浩司, 前門戸任, 貫和敏博

    日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.O2-13-2　2015

  35. ACTH産生腫瘍が疑われた肺小細胞癌の1例

    盛田麻美, 福原達朗, 鈴木綾, 渡邉香奈, 前門戸任, 突田容子, 伊藤しげみ, 佐藤郁郎

    肺癌(Web)　55　(4)　288(J‐STAGE)　2015

    ISSN： 1348-9992

  36. 高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定とEGFR‐TKI効果との関連性の検討

    渡辺香奈, 福原達朗, 小林真紀, 突田容子, 盛田麻美, 鈴木綾, 田中伸幸, 寺崎浩司, 前門戸任, 貫和敏博

    日本肺癌学会総会号　55th　388　2014/10/05

    ISSN： 0386-9628

  37. EGFR遺伝子変異陽性肺癌患者に対するSecond‐TKIの開始時期と治療効果の検討

    福原達朗, 渡邉香奈, 鈴木綾, 盛田麻美, 突田容子, 前門戸任

    日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P2-18-5　2014

  38. Crizotinibによる食道炎を繰り返し発症し,隔日投与で治療継続が可能であった肺腺癌の1例

    小林真紀, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 渡邉香奈, 前門戸任, 野口哲也

    肺癌(Web)　54　(6)　867(J-STAGE)　2014

    ISSN： 1348-9992

  39. A CASE OF SMALL CELL LUNG CANCER WITH CANCER-ASSOCIATED RETINOPATHY ( CAR) ACCOMPANIED BY CIRCULATING ANTI-CRMP5/CV2 ANTIBODIES

    Mami Morita, Tatsuro Fukuhara, Yoko Tsukita, Zenta Watanuki, Aya Suzuki, Kana Watanabe, Nobuyuki Sato, Hidetoshi Takahashi, Shigemi Ito, Ikuro Sato, Makoto Maemondo

    RESPIROLOGY　18　8-8　2013/11

    ISSN： 1323-7799

    eISSN： 1440-1843

  40. EGFR遺伝子変異陽性患者に対するSecond‐TKIのタイミングとその治療成績

    福原達朗, 渡邉香奈, 盛田麻美, 突田容子, 綿貫善太, 鈴木綾, 前門戸任

    日本肺癌学会総会号　54th　601　2013/10/05

    ISSN： 0386-9628

  41. 非小細胞肺癌脳転移マネージメント:MRI検査間隔による放射線治療方法の変化

    渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 綿貫善太, 鈴木綾, 松原信行, 前門戸任

    日本臨床腫瘍学会学術集会(CD-ROM)　11th　ROMBUNNO.O3-077　2013

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Research Projects 2

  1. 免疫抵抗性克服のための非小細胞肺癌における放射線照射がもたらす免疫応答の解析

    突田 容子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    進行期非小細胞肺がんに対して、薬物療法（免疫療法＋殺細胞性抗癌薬）に放射線照射（姑息照射）を追加していた13例、放射線照射を施行していない薬物療法のみの6例、の治療開始前後の血漿と末梢血単核細胞を解析した。フローサイトメトリーにより、末梢血単核細胞中のT細胞（CD4陽性T細胞、CD8陽性T細胞）、B細胞、骨髄由来抑制細、NK細胞、特にT細胞ではメモリーT細胞や疲弊T細胞、制御性T細胞、に分類して、免疫細胞の数と割合を解析した。収集した臨床情報と紐づけて解析を行った。放射線照射の有無による変化は現時点では明らかではないが、奏効例と非奏功例やPFSの比較において、奏功例や長期奏功例で治療前に有意に増加している細胞分画を同定した。これらの細胞分画は複合免疫療法における効果予測因子となりうるため、さらなる検証を行っていく。 血漿のサイトカインやケモカインをLEGENDplexTM multiplex Assayにて13種類を測定した。奏功例では治療前の炎症性サイトカインであるTNFαなどが治療開始前の時点ですでに増加していることが分かった。先述した細胞分画と関連のあるサイトカインについても検証を進めている。 放射線照射ではDAMPsが放出されるとの既報から、血漿中のDAMPs（HMGB1、カルレティキュリン）を測定したが、こちらは奏功例と非奏功例や放射線照射の有無における有意差を認めなかった。

  2. The role of reactive sulfur species and cysteinyl-tRNA synthetase2 in lung cancer

    Tsukita Yoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2019/04/01 - 2020/03/31

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    Cysteinyl-tRNA synthetase (CARS)2 is known as a novel cysteine hydropersulfide synthase. In our lung cancer tissue biobank, CARS2 mRNA expression decreased in cancer tissues compared to normal tissues. The protein expression of CARS2 in relapsed cancers tended to be lower than in non-relapsed cancers. CARS2 expression significantly correlated with expression of genes encoding other enzymes involved in sulfur metabolism. These data suggest that sulfur metabolis is associated with the carcinogenesis and cancers vary in their dependence on sulfur metabolism.