Basic Research on Novel Treatment for Dialysis Kidney Cancer Using Immune Checkpoint Molecular Antibodies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16807
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Keio University
• Principal Investigator: Takamatsu Kimiharu 慶應義塾大学, 医学部(信濃町), 共同研究員 (00649874)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腎細胞癌 / 腫瘍免疫微小環境 / LAG-3 / TIM-3 / TIGIT / 免疫チェックポイント阻害剤

Outline of Final Research Achievements

After evaluating the immune microenvironment in hemodialysis renal cell carcinoma, we found that PDL1 expression was higher in HD-renal carcinoma than in normal-type clear cell renal cell carcinoma, and reported this finding at the japanese pediatric urology annual conference.
Furthermore, in the process of analyzing the tumor immune microenvironment, PD-1/PD-L1 inhibitor-resistant cases have been became clinical unmet needs. Therefore, focusing on the expression status of next-generation checkpoint molecules, LAG-3, TIM-3, and TIGT, we found that the three molecules are mutually exclusive in renal cell carcinoma and that the background of the mutation is p53 gene mutation. We constructed and reported a new classification of renal cell carcinoma using these three novel molecules.

Free Research Field

腎細胞癌

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかになった透析腎癌の免疫環境の特徴は透析腎癌において免疫チェックポイント阻害剤の効果が高いことを示唆するものであり、臨床上有意義である。
また、次世代チェックポイント分子が腎細胞癌で相互排他性を示すことは、現在開発中の次世代免疫チェックポイント阻害剤の治療薬選択につながる可能性があり、テイラーメイド医療による薬剤の有効性の最大化につながる。さらに、高額な新規薬剤の有効利用の点から医療経済への寄与が期待される。