Acquisition of basic data on cancer antigens for the development of vaccine therapies for lung cancer.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16380
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Gifu University
• Principal Investigator: Komuro Hiroyasu 岐阜大学, 医学部附属病院, 医員 (40839122)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん・精巣抗原 / エキソームシーケンス / RNAシーケンス / TIL / RT-PCR法 / Single Cell解析 / 発現差解析

Outline of Final Research Achievements

In this study, freshly isolated cancer cells were collected from three lung cancer specimens, from which CD8+T cells were isolated and analyzed for T cell RNA expression and T cell receptor (TCR) genes using single cell analysis. On the other hand, DNA and RNA were extracted from the tumor cells of the same three cases, and cancer antigens were predicted using AI. By combining both information, tumor-specific T cell populations, and cancer antigens were identified.
49 TCRs in the T cell cluster expressing exhaustion markers such as ENTPD1 (CD39), PDCD1 (PD1), and HAVCR2 (TIM3) were validated, and 9 TCRs were found to react with cancer antigens, suggesting that it was a tumor-specific cluster. Seven cancer antigens were confirmed to be reactive.

Free Research Field

腫瘍免疫学、呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

肺癌に対する個別化がんワクチン開発の際に、腫瘍反応性CD8+T細胞が認識するがん抗原に優先順位がつけることができれば、より効果的なワクチン療法を提案できる可能性がある。がん抗原の候補として遺伝子変異由来のネオ抗原とがん・精巣抗原（KK-LC-1）を含めて検討しており、TCRとがん抗原のペアで反応性を検証できたことで、抗原ごとの反応性の違いを検証することができた。これはがん抗原の順位づけの一助となる可能性があり、将来の肺癌に対するがんワクチンを開発する上で重要な情報となる。