Comprehensive analysis of the association of treatment efficacy from immune checkpoint inihibitors with host-HLA and tumor environment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Kondo Tsunenori 東京女子医科大学, 医学部, 教授 (50301544)
• Co-Investigator(Kenkyū-buntansha): 雑賀 寛 東京女子医科大学, 医学部, 非常勤講師 (10815004) ; 福田 洋典 東京女子医科大学, 医学部, 助教 (60848951)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腎癌 / HLA / 腫瘍微小環境 / 免疫細胞 / 網羅的遺伝子発現解析

Outline of Final Research Achievements

In this study, we analyzed whether HLA (human leukocyte antigen) and the tumor microenvironment correlate with the efficacy of immune checkpoint inhibitors (ICIs). We extracted DNA from peripheral blood of 39 cases of renal cell carcinoma patients treated with ICIs and performed HLA typing using next-generation sequencing. By analyzing the correlation between this data and treatment outcomes and prognosis information, we were able to identify HLA-C subtypes associated with treatment efficacy. Furthermore, by analyzing tumor-infiltrating immune cells using flow cytometry and integrating with ICI treatment outcomes, we suggested that ICIs have a higher treatment efficacy in cases with abundant immune cell infiltration.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

この研究の社会的意義は、ICI治療におけるHLAと腫瘍微小環境の重要性を明らかにすることで今後の個別化されたがん治療に向けた情報として重要な点にある。特定のHLAサブタイプや免疫細胞浸潤の程度が治療効果に影響を与える可能性を示し、将来的にはICI治療の効果を最大化し、患者の生活の質を向上させる治療戦略を開発する基盤を提供することが期待される。