Analysis of PD-1+ tumor-infiltrating T cells according to cancer antigen hierarchy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03694
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Okayama University (2021-2022); Chiba Cancer Center (Research Institute) (2020)
• Principal Investigator: Togashi Yosuke 岡山大学, 医歯薬学域, 教授 (80758326)
• Co-Investigator(Kenkyū-buntansha): 盛永 敬郎 千葉県がんセンター(研究所), がん治療開発グループ 細胞治療開発研究部, 研究員 (30757000)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腫瘍免疫 / ネオ抗原 / PD-1 / 制御性T細胞

Outline of Final Research Achievements

Cancer is believed to exist as "cancer" by escaping from antitumor immunity using suppressive molecules and/or suppressive cells such as PD-1/PD-L1 and regulatory T cells (Treg). Since anti-PD-1/PD-L1 antibodies exert their effects by activating the effector capacity of T cells, responders to anti-PD-1/PD-L1 antibodies had high frequency of PD-1+ effector T cells in the tumor microenvironment. Such T cells recognized neoantigens. In contrast, PD-1+ Tregs highly infiltrated in resistant patients. We have shown that suppressiive functuons of PD-1+ Tregs are activated by PD-1 blockade. Furthermore, a specific metabolic environment was involved in PD-1 expression in Tregs.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

腫瘍浸潤PD-1陽性エフェクターT細胞ががん免疫療法の効果に関与し、同時にPD-1陽性Tregが耐性に関与することを明らかにでき、効果予測を正確に行えるようになった。また、新たにPD-1陽性Tregが標的となり得て、そこに代謝環境が関与するため、代謝による制御も新たなコンセプトの治療になり得ると考えられた。これらはがん免疫療法のさらなる治療成績の向上に繋がると考えている。