Identification of tumor microenvironment involving tumor infiltrating regulatory T cells in lung cancer

• Project/Area Number: 16K21533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; Tumor biology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Kurose Koji 川崎医科大学, 医学部, 助教 (30551139)
• Research Collaborator: Ohue Yoshihiro 川崎医科大学, 医学部, 講師 (70435014) ; Nakayama Eiichi 川崎医科大学, 客員教授 (60180428) ; Oka Mikio 川崎医科大学, 医学部, 教授 (40223995)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肺癌微小環境 / 制御性T細胞 / Treg / PD-L1 / PD-1 / TIM-3 / 腫瘍浸潤リンパ球 / 非小細胞肺癌 / 肺がん

Outline of Final Research Achievements

In this study, in order to clarify the presence or absence of inflammation of the tumor microenvironment and the involvement of tumor infiltrating regulatory T cells (Treg) in lung cancer, we examined the association of tumor infiltrating lymphocytes, Treg fraction, and inhibitory molecules PD-1, TIM-3 on T-cells with PD-L1 on tumor cells. In the high expression group of PD-L1, there were many tumor infiltrating lymphocytes, whereas there were also many activated Tregs, and high expression of PD-1 and TIM-3 on T cells was observed. Furthermore, Treg depletion using anti-CCR4 antibody resulted in an increase in the number of tumor infiltrating lymphocytes and an increase in the expression of PD-L1 on tumor cells. In the high expression group of PD-L1, Treg depletion and anti-PD-1 therapy may enhance the therapeutic effect.

Research Products

• [Journal Article] NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC (2017)
  • Author(s): Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, Sato E, Isobe M, Kanazawa T, Matsumoto M, Iwahori K, Kawashima A, Morimoto-Okazawa A, Nishikawa H, Oka M, Pan L, Venhaus R, Nakayama E, Mori M, Doki Y, Wada H.
  • Journal Title: J Immunother Volume: epub Issue: 4 Pages: 140-147
  • DOI: 10.1097/cji.0000000000000162
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nivolumab-induced polyarthritis. (2017)
  • Author(s): Kodama S, Kurose K, Mukai T, Morita Y.
  • Journal Title: BMJ Case Rep. Volume: - Pages: bcr-2017-223387
  • DOI: 10.1136/bcr-2017-223387
  • Peer Reviewed
• [Journal Article] Survival of Lung Adenocarcinoma Patients Predicted from Expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on Tumor Cells and Tumor-Infiltrating T Cells. (2016)
  • Author(s): Ohue Y, Kurose K, Nozawa R, Isobe M, Nishio Y, Tanaka T, Doki Y, Hori T, Fukuoka J, Oka M, Nakayama E
  • Journal Title: Cancer Immunology Research Volume: 4 Pages: 1049-1060
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Reviving chemotherapy sensitivity after anti-CCR4 mAb (mogamulizumab) treatment in lung cancer patients (2018)
  • Author(s): 黒瀬 浩史, 大植 祥弘, 磯辺 みどり, 鈴木 進, 和田 尚, 上田 龍三, 中山 睿一, 岡 三喜男
  • Organizer: 第15回日本免疫治療学研究会学術集会
• [Presentation] Reviving chemotherapy sensitivity after anti-CCR4 mAb (mogamulizumab) treatment in lung cancer patients (2017)
  • Author(s): Kurose K, Ohue Y, Isobe M, Suzuki S, Wada H, Oka M, Ueda R, Nakayama E.
  • Organizer: Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
  • Int'l Joint Research
• [Presentation] Reviving chemotherapy sensitivity after anti-CCR4 mAb (mogamulizumab) treatment in lung cancer patients (2017)
  • Author(s): Koji Kurose, Yoshihiro Ohue, Midori Isobe, Susumu Suzuki, Hisashi Wada, Ryuzo Ueda, Eiichi Nakayama and Mikio Oka
  • Organizer: IASLC 18th world conference on lung cancer(WCLC 2017)
  • Int'l Joint Research
• [Presentation] 肺腺癌のTIM-3/Galectin-9経路を介した免疫抑制と予後 (2016)
  • Author(s): 黒瀬 浩史
  • Organizer: 第57回日本肺癌学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）