Investigation of the immune response of the tumor-infilteating T cells by novel scTCR-seq methods

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16620
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Shichino Shigeyuki 東京理科大学, 研究推進機構生命医科学研究所, 助教 (70822435)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: T細胞応答 / TCRレパトワ解析 / single-cell TCR-seq / single-cell RNA-seq

Outline of Final Research Achievements

We have succeeded in establishing a unique and highly accurate scTCR-seq analysis method based on BD Rhapsody. When a B16 mouse subcutaneous tumor model administered with anti-CD4 antibody was analyzed by this method, eight major infiltrating T cell subsets were identified based on gene expression. Of the oligoclonal / polyclonal T cell fractions identified by overlapping analysis of scTCR-seq information and regional lymph node TCR-seq information, the proportion of ealry-exhausted T cells and late-exhausted T cells was 10%: 90% for the former and the latter. Was 30%: 70%. In addition, the latter expressed significantly more genes involved in the phenotype of early-exhausted T cells than the former.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、腫瘍浸潤T細胞のうち、Oligoclonal画分ではなく、Polyclonal画分に分化・増殖ポテンシャルを持つ前期疲弊T細胞が維持されていることが見出された。近年, 抗PD-1抗体を投与された皮膚基底細胞癌症例において, 後期疲弊T細胞からなる腫瘍浸潤T細胞クローンが治療前後で入れ替わっていることが報告されている。本研究やこれらの報告を鑑みると、当該Polyclonal画分に属するT細胞クローンが, より反応性が高いOligoclonal画分のT細胞クローンを置換し, 新たな腫瘍反応性クローンとして機能し、チェックポイント阻害剤はそれを増強しているという可能性が考えられる。