Clinicopathological analysis of expression of immune checkpoint molecules in patient with resected lung cancer

• Project/Area Number: 26462144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: National Hospital Organization, Kyushu Cancer Center
• Principal Investigator: Mitsuhiro Takenoyama 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 呼吸器腫瘍科部長 (10309966)
• Co-Investigator(Kenkyū-buntansha): 一瀬 幸人 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 臨床研究センター長 (00450940) ; 豊川 剛二 九州大学, 医学研究員, 助教 (30627261)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 免疫チェックポイント / 呼吸器悪性腫瘍 / PD-1 / driver mutation

Outline of Final Research Achievements

A new immunological therapy using by immune checkpoint inhibitors has developed as a standard therapy against advanced non-small cell lung cancer recently. In this study, to elucidate the clinicopathological significance of PD-L1 expression in lung cancer tissues, its expression was analyzed together with oncogenic drivers such asn EGFR and EML4-ALK in the resected specimens from patients with p-stage I adenocarcinoma. Higher expression of PD-L1 was found in 32% out of 228 patients. Low expression of PD-L1 is a poor prognostic marker in patients with EGFR wild type, and is an independent poor prognostic marker in patients with stage IB.

Research Products

• [Journal Article] Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma (2016)
  • Author(s): Ohba T, Toyokawa G, Osoegawa A, Hirai F, Yamaguchi M, Taguchi K, Seto T, Takenoyama M,
  • Journal Title: Surg Today Volume: 46 Issue: 9 Pages: 1091-1098
  • DOI: 10.1007/s00595-015-1295-z
  • Peer Reviewed
• [Journal Article] Post-recurrence survival of elderly patients 75 years of age or older with surgically resected non-small cell lung cancer (2016)
  • Author(s): Takenaka T, Inamasu E, Yoshida T, Toyokawa G, Nosaki K, Hirai F, Yamaguchi M, Seto T, Takenoyama M, Ichinose Y
  • Journal Title: Surg Today Volume: 46 Issue: 4 Pages: 430-436
  • DOI: 10.1007/s00595-015-1200-9
  • Peer Reviewed
• [Journal Article] Pulmonary resection for synchronous M1b-cstage IV non-small cell lung cancer patients (2016)
  • Author(s): Yamaguchi M, Edagawa M, Suzuki Y, Toyozawa R, Hirai F, Nosaki K, Seto T, Takenoyama M, Ichinose Y
  • Journal Title: Ann Thorac Surg Volume: 103(5) Issue: 5 Pages: 1594-1599
  • DOI: 10.1016/j.athoracsur.2016.08.098
  • Peer Reviewed
• [Journal Article] Current Organ Topics Thorax/Lung and Mediastinum:Pleura Cancer 肺癌 肺腺癌のT因子 総括 (2016)
  • Author(s): 竹之山光広、一瀬幸人
  • Journal Title: 癌と化学療法 Volume: 43(8) Pages: 953-954
• [Journal Article] Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. (2016)
  • Author(s): Toshio Shimizu,corresponding author Takashi Seto, Fumihiko Hirai, Mitsuhiro Takenoyama, Kaname Nosaki, Junji Tsurutani, Hiroyasu Kaneda, Tsutomu Iwasa, Hisato Kawakami, Kazuo Noguchi, Takashi Shimamoto, and Kazuhiko Nakagawa
  • Journal Title: Invest New Drugs Volume: 34(3) Issue: 3 Pages: 347-54
  • DOI: 10.1007/s10637-016-0347-6
  • Peer Reviewed
• [Journal Article] Experience with erlotinib in lung adenocarcinoma harboring a coexisting KIF5B-RET fusion gene and EGFR mutation: report of a rare case (2014)
  • Author(s): Hirai F, Takenoyama M, Taguchi K, Toyozawa R, Inamasu E, Toyokawa G, Yoshida T, Shiraishi Y, Takenaka T, Yamaguchi M, Ushijima C, Seto T, Takeo S, Ichinose Y
  • Journal Title: J Thorac Oncol Volume: 9(5) Issue: 5 Pages: e37-e39
  • DOI: 10.1097/jto.0000000000000097
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic and therapeutic implications of aromatase expression in lung adenocarcinomas with EGFR mutations. (2014)
  • Author(s): Kohno M, Okamoto T, Suda K, Shimokawa M, Kitahara H, Shimamatsu S, Konishi H, Yoshida T, Takenoyama M, Yano T, Maehara Y.
  • Journal Title: Clinical Cancer Research Volume: 20 Issue: 13 Pages: 3613-22
  • DOI: 10.1158/1078-0432.ccr-13-2683
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of detecting somatic gene mutations in surgically resected adenosquamous cell carcinoma of the lung in Japanese patients (2014)
  • Author(s): Morodomi Y, Okamoto T, Takenoyama M, Takada K, Katsura M, Suzuki Y, Fujishita T, Kitahara H,
  • Journal Title: Ann Surg Oncol Volume: in press Issue: 8 Pages: 2593-8
  • DOI: 10.1245/s10434-014-4218-0
  • Peer Reviewed / Open Access
• [Journal Article] Secondary Mutations at I1171 in the ALK Gene Confer Resistance to Both Crizotinib and Alectinib (2014)
  • Author(s): Toyokawa G, Hirai F, Inamasu E, Yoshida T, Nosaki K, Takenaka T, Yamaguchi M, Seto T,
  • Journal Title: J Thorac Oncol Volume: 9(12) Issue: 12 Pages: e86-e87
  • DOI: 10.1097/jto.0000000000000358
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancerdagger (2014)
  • Author(s): Takenaka T, Takenoyama M, Yamaguchi M, Toyozawa R, Inamasu E, Kojo M, Toyokawa G, Yoshida T, Shiraishi Y, Morodomi Y, Hirai F, Taguchi K, Shimokawa M, Seto T, Ichinose Y
  • Journal Title: Eur J Cardiothorac Surg Volume: 47(3) Issue: 3 Pages: 550-555
  • DOI: 10.1093/ejcts/ezu227
  • Peer Reviewed / Open Access
• [Presentation] ニボルマブの投与後の無治療経過観察中に、長期の病状安定が得られた肺癌の一例 (2017)
  • Author(s): 原武直紀、枝川真、島松晋一郎、豊澤亮、平井文彦、野崎要、山口正史、瀬戸貴司、竹之山光広、一瀬幸人
  • Organizer: 第57回日本肺癌学会九州支部学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2017-02-24
• [Presentation] Nivolmab投与で特異な免疫関連有害事象を示した肺癌2症例 (2017)
  • Author(s): 島松晋一郎、山口正史、枝川真、豊澤亮、野崎要、平井文彦、瀬戸貴司、竹之山光広、一瀬幸人
  • Organizer: 第57回日本肺癌学会九州支部学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2017-02-24
• [Presentation] 当院でのNivolumab による治療症例の検討 (2016)
  • Author(s): 枝川真、鈴木雄三、島松晋一郎、豊澤亮、野崎要、平井文彦、山口正史、瀬戸貴司、竹之山光広、一瀬幸人
  • Organizer: 第57回日本肺癌学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-12-19
• [Presentation] 当院における免疫細胞療法（先進医療B）を円滑に遂行するための多職種医療チームの構築 (2016)
  • Author(s): 和田龍昇、渕脇菜保子、中村由美子、植村直美、沖山倫子、川上恵子、荒巻聖、花田博文、勝木成将、中村弘子、矢野智英、佐藤孝光、宅間奈緒美、北里謙二、田口健一、末廣陽子、竹之山光広、一瀬幸人、江崎泰斗
  • Organizer: 第70回国立病院総合医学会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-11-11
• [Presentation] 日本人非小細胞肺癌に対する抗PD-1抗体nivolumabの第II相試験 (2015)
  • Author(s): 安宅信二，西尾誠人，樋田豊明，中川和彦，酒井洋，野上尚之，高橋利明，軒原浩，坂英雄， 竹之山光広，藤田史郎，田中洋史，武田晃司，里内美弥子，磯部宏，前門戸任，後藤功一， 平島智徳，湊浩一，田村友秀
  • Organizer: 第56回日本肺癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-11-26
• [Presentation] ALK阻害剤に対する耐性獲得症例の検討 (2014)
  • Author(s): 豊川剛二、稲益栄子、吉田月久、野崎要、竹中朋祐、平井文彦、山口正史、瀬戸貴司、竹之山光広、一瀬幸人
  • Organizer: 第55回日本肺癌学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] 悪性胸膜中皮腫における線溶系分子の発現と臨床病理学的因子に関する検討 (2014)
  • Author(s): 諸富洋介、岡本龍郎、高田和樹、桂正和、鈴木雄三、藤下卓才、北原大和、島松晋一郎、田川哲三、岡野慎士、田口健一、竹之山光広、一瀬幸人、前原喜彦
  • Organizer: 第55回日本肺癌学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] 遺伝子変異検索を目的とした手術の検討 (2014)
  • Author(s): 稲益 英子、吉田 月久、豊川 剛二、野崎 要、竹中 朋祐、平井 文彦、山口 正史、瀬戸 貴司、竹之山 光広、一瀬 幸人
  • Organizer: 第31回日本呼吸器外科学会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 75 歳以上高齢者非小細胞肺癌術後再発症例の治療成績 (2014)
  • Author(s): 竹中 朋祐、稲益 英子、吉田 月久、豊川 剛二、野崎 要、平井 文彦、山口 正史、瀬戸 貴司、竹之山 光広、一瀬 幸人
  • Organizer: 第31回日本呼吸器外科学会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 胸腔鏡下肺部分切除によりc kit 遺伝子変異が確認された胸腺癌の一例 (2014)
  • Author(s): 稲益英子、豊澤亮、豊川剛二、白石祥理、竹中朋祐、平井文彦、山口正史、瀬戸貴司、 竹之山光広、一瀬幸人
  • Organizer: 第37回日本呼吸器内視鏡学会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-14 – 2014-04-15