Identification of tumor-specific antigens to construct the novel combination immunotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08711
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Hazama Shoichi 山口大学, 医学部, 特別医学研究員 (50253159)
• Co-Investigator(Kenkyū-buntansha): 永野 浩昭 山口大学, 大学院医学系研究科, 教授 (10294050) ; 鈴木 伸明 山口大学, 大学院医学系研究科, 講師 (50526910) ; 松井 洋人 山口大学, 医学部附属病院, 助教 (60780781) ; 恒富 亮一 山口大学, 医学部附属病院, 講師 (10420514) ; 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 癌

Outline of Final Research Achievements

The immunogenicity of neoantigen peptides in colorectal cancer (n=6), including a TMB-high case, was evaluated. The results showed that neoantigen peptides in the TMB-high case showed higher immunogenicity. Comparison between primary and liver metastases showed that about 70% of the mutations were common, and about 30% were identified only in primary tumors and disappeared in metastases. Only about 3% of mutations were newly identified only in liver metastases. Neoantigen peptides common to both primary and metastases were shown to have low immunogenicity. Neoantigen peptides with markedly higher immunogenicity were found only in the primary tumor, and a neoantigen peptide/TCR complex was also detected in the PBMCs.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

大腸癌肝転移において、原発巣・転移巣のどちらからも検出されるネオアンチゲンについては免疫原性が強く抑制されている可能性が示唆された。臨床応用には、高免疫原性ネオアンチゲン同定のワークフローの確立だけでなく、免疫原性抑制解除の必要性が示された。