The nature of exhausted CD4+ T cells in the tumor microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20824
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Okayama University
• Principal Investigator: Nagasaki Joji 岡山大学, 医歯薬学域, 研究准教授 (20955447)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 濾胞性ヘルパーT細胞 / 腫瘍微小環境 / 疲弊 / 腫瘍特異的T細胞 / 細胞傷害性T細胞

Outline of Final Research Achievements

We found a novel population of cytotoxic TFH-like cells in TME, which directly attack tumor cells. Comparing the gene expression between the conventional non-cytotoxic TFH and the novel cytotoxic TFH-like cells, we identified the former showed TCF1 high and BLIMP1 low phenotypes, while the latter TCF1 low and BLIMP1 high, which are similar to progenitor exhaustion/ terminally differentiated exhaustion in CD8+ T cells. The in vitro functional analysis showed that TCF1 over-expressed or BLIMP1 knocked down TFH cells secreted a smaller volume of granzyme B, which suggests the concept is similar to that of CD8+ T cell exhaustion.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

本研究ではTMEのTFHの中に細胞傷害活性を有するTFH様細胞が存在することを新たに見出し、従来型TFHと細胞傷害性TFH様細胞とは、CD8陽性T細胞におけるprogenitor exhaustion とterminally differentiated exhaustionの関係と同様であることを明らかにした。本研究により今まで明らかではなかったCD4陽性T細胞におけるexhaustionを再定義することができ、抗腫瘍免疫応答の本体解明、新規バイオマーカーの同定やCAR-T療法などの細胞療法含む新規治療開発に繋がると考えている。