Identification of T cell receptor repertoire profiling that define lung cancer risk

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19492
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shiraishi Kouya 国立研究開発法人国立がん研究センター, 研究所, 部門長 (80609719)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 肺がん / 生殖細胞系列変異 / TCRレパトア解析

Outline of Final Research Achievements

We identified 19 LADC susceptibility loci, including several variants in the major histocompatibility complex region. The class I HLA-A*24:02 allele was identified as a risk factor for LADC and as conferring attenuated immunity. HLA-A*24:02 binds fewer somatic mutation-derived neoantigens in tumour cells than other HLA-A proteins, and loss of this allele occurs infrequently.
Next, we examined the correlation between T-cell receptor diversity (TCR repertoire profile) and lung cancer risk, especially for HLA risk alleles. Using approximately 2,500 RNA sequencing data obtained from previously acquired lung adenocarcinoma tissue specimens, we conducted the study using the MIXCR. We examined whether the RNA sequencing methods had any effect on the TCR repertoire profile, and we were able to detect the TCR repertoire profile, and we performed an integrated analysis focusing on the diversity of HLA alleles and TCR repertoire profile. The results are now being compiled.

Free Research Field

がんゲノム解析

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、様々な遺伝要因や環境要因等により免疫の活性化能に影響を与え、発がんリスクに寄与している可能性が示された。現在TCRレパトアの多様性は、免疫チェックポイント阻害剤など、一部の薬剤の治療効果や副作用等に影響を与えていることが報告されていることから、今後も重要な研究テーマであると考えられる。