Immunogenic characteristics of microsatellite instability-low esophagogastric junction adenocarcinoma based on clinicopathological, molecular, immunological and survival analyses

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09046
• 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: Japanese Foundation for Cancer Research
• Principal Investigator: IMAMURA Yu 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (70583045)
• Co-Investigator(Kenkyū-buntansha): 森 誠一 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814) ; 清谷 一馬 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 主任研究員 (30433642)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 食道胃接合部腺癌 / マイクロサテライト不安定性 / 腫瘍免疫

Outline of Final Research Achievements

MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82;
P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

食道胃接合部腺癌を題材に、MSI-L腫瘍の臨床病理学的および分子生物学的特徴を解析し、MSI-L腫瘍が免疫原性腫瘍であることを明らかにした。本研究の結果は、癌腫を問わず同様の特徴を示す可能性がある。さらに、MSI-L腫瘍に関する新たな免疫治療研究の開発と臨床応用への展開を促進する足掛かりとなるデータであるといえる。