Single cell analysis of tumor-microenvironment based on TIL functions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03460
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: HIROHASHI Yoshihiko 札幌医科大学, 医学部, 准教授 (30516901)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腫瘍微小環境 / 細胞傷害性T細胞 / 腫瘍抗原 / 1細胞解析

Outline of Final Research Achievements

In this study, we analyzed melanoma cases that were treated by PD-1 blockade and resulted in reflactory for PD-1 blockade. Tumor infiltrating lymphocytes (TILs) were analyzed by single cell RNA-sequence. T cell receptor (TCR) transduced T (TCR-T) cells were generated according to the TCR sequences and tested the specificity for autologous melanoma cells. Surprisingly, most TCR-T cells recognized melanoma cells indicating TILs were functional, but PD-1 blockade did not work. These result indicate that there are other immune escape mechanisms beside PD-L1/PD-1.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、悪性黒色腫症例の腫瘍浸潤リンパ球を1細胞遺伝子発現解析行った。その結果、免疫チェックポイント阻害剤(PD-1阻害剤）不応性症例の腫瘍浸潤リンパ球であっても、腫瘍細胞を認識しうることを見出した。この結果は、PD-L1/PD-1阻害治療抵抗性症例であっても、免疫療法が効く可能性を示すと同時に、PD-L1/PD-1以外の免疫チェックポイント等の免疫抑制機構が存在する事を示唆する。この解析を進める事により、PD-1阻害療法の適応を定義出来ると同時に、新たな治療法開発への rationale となる。