Comprehensive analysis of T cell inflamed phenotypes in esophageal cancer for the development of new biomarkers

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16476
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Yagi Taisuke 熊本大学, 大学院生命科学研究部(医), 特定研究員 (60836253)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 胃癌 / 遺伝子解析 / 性差

Outline of Final Research Achievements

Whole genome sequencing of gastric cancer revealed that TP53 mutations were significantly more common in males, and CDH1, PIK3CA, ERBB3, TRRAP and KRAS mutations were significantly more common in females.
When classified into T cell inflamed phenotypes and non T cell inflamed phenotypes, survival outcomes for T-cell inflamed phenotypes were significantly worse in females than males.
In order to clarify why survival outcome differ according to gender, we searched for genes whose expression was significantly elevated in the T cell inflamed phenotype, and found a gender difference in the expression of CCL18 and CD8.

Free Research Field

消化器癌、遺伝子解析

Academic Significance and Societal Importance of the Research Achievements

本研究で、胃癌において抗腫瘍免疫の作用に性差があることが示唆された。様々な癌腫で免疫チェックポイント阻害剤が有効な治療手段として認識され実臨床でも使用されているが、免疫チェックポイント阻害剤を使用しても有効な治療効果を得られない症例も多い。本研究は胃癌における抗腫瘍免疫に男女で性差がある可能性を示唆しており、今後様々な癌腫で研究が進むことで今後の化学療法における個別化治療の発展のための礎となる研究となりうる可能性がある。