Immune response of tumor-infiltrating T lymphocytes in sarcoma using single-cell analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22980
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Sapporo Medical University
• Principal Investigator: MURATA Kenji 札幌医科大学, 医学部, 特任助教 (80722454)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 骨軟部肉腫 / 肉腫抗原 / T細胞受容体 / 腫瘍浸潤Tリンパ球 / シングルセル解析

Outline of Final Research Achievements

We isolated tumor-infiltrating lymphocytes (TILs) from a myxoinflammatory fibroblastic sarcoma tissue and performed single-cell analyses of the TILs. CD8+ T cells were dominant in the TILs, and top two T-cell receptors (TCRs) were more than 40% of CD8+ T cells. CD8+ TILs of high TCR clonality did not express memory markers, but highly expressed exhaustion markers, activation makers, and cytokine genes, suggesting that these TCRs might recognize tumors.

Free Research Field

骨軟部肉腫、腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

骨軟部肉腫（以下、肉腫）はまれな悪性腫瘍だが、化学療法不応例の予後は不良である。肉腫に対する養子免疫療法の適応を広げ奏功率を向上させるためには、新たな肉腫特異抗原とそれに反応する抗腫瘍効果の高いT細胞受容体（TCR）の同定が必要と考えられる。我々は、粘液炎症性線維芽細胞肉腫に浸潤したリンパ球を単細胞レベルで解析し、腫瘍に反応する可能性が高い2種類のTCRを単離した。現在、その認識抗原を探索している。