Molecular biological analysis of disorders of energy metabolism and mechanisms of Immune Escape in cancer in renal cell carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09546
• 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: Dokkyo Medical University
• Principal Investigator: kamai takao 獨協医科大学, 医学部, 教授 (80316562)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腎細胞癌 / FH / SDH / HLRCC / Keap1 / Nrf2

Outline of Final Research Achievements

We reported (1）Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer diferentiation and local invasion. (2）This study assessed the role of SDHA gene mutations in human RCC. Targeted next-generation sequencing and direct Sanger sequencing revealed single nucleotide variants (SNVs) of the SDHA gene with amino acid sequence variations in 11/129 tumors, while no SDHB/C/D gene mutations were found. Tumor cells with SNVs of the SDHA gene were characterized by eosinophilic cytoplasm and various patterns of proliferation.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

(1）腫瘍微小環境におけるPD-L1の発現とthe tumor-infltrating lymphocyte density (TILD)がupper urinary tract urothelial carcinoma (UTUC)の進行に影響を与えることを示した。したがって、この癌のより効果的な治療戦略を開発するには、腫瘍微小環境の免疫学的特性を解明する重要性を明らかにした。(2）この研究では、SDH欠損腎細胞癌(RCC)においてはSDHA遺伝子の一塩基変異体(SNVs)が129例中11例に検出され、SDHB/C/D遺伝子変異は検出されないことを明らかにした。