Construction of non-clinical model corresponding to the metastatic urothelial carcinoma classified based on immune environment and molecular diagnosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16776
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: University of Tsukuba
• Principal Investigator: Kawahara Takashi 筑波大学, 医学医療系, 助教 (50758919)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 膀胱癌 / がん免疫環境 / FGF-FGFRシグナル / 体細胞変異 / 分子分類

Outline of Final Research Achievements

To elucidate the relationship between somatic mutations and tumor immune environment in bladder cancer, we analyzed bladder cancer tissues of 103 bladder cancer patients. We compared the relationship tumor characteristics with tumor immune environment. There were less CD8 positive infiltrating cells in FGFR3 mutation than in FGFR3 wild cases. There were more CD8 positive cells in TP53 mutation than TP53 wild cases. In molecular subtype, there were few CD8 positive infiltrating cells in basal type than in luminal type. Next, focusing on FGFR signals, FGFR3 expression was frequently found in low grade and low stage, and FGFR1 expression was in high grade and high stage. FGFR1 overexpression case showed high infiltration of CD8 positive T cells. We found that somatic mutations, molecular subtype and different activation of FGFR signals have different immune environments in bladder cancer.

Free Research Field

泌尿器科領域

Academic Significance and Societal Importance of the Research Achievements

近年膀胱癌でも免疫チェックポイント阻害剤が臨床応用されているが腫瘍内免疫環境の状態によって同薬剤の反応性が異なることが示されている。しかし、がん細胞の遺伝子変異や分子分類での腫瘍内免疫環境の関連は明らかとなっていない。今回の研究では体細胞変異および分子分類と腫瘍内免疫環境との関連に着目し、膀胱癌においてFGFR3遺伝子に変異を有する患者さんでは腫瘍細胞への免疫細胞浸潤が少なくTP53遺伝子に変異を有する患者さんでは腫瘍細胞への免疫細胞浸潤が多いことがわかった。また分子分類の違いにより免疫細胞浸潤が異なることを明らかとした。これらの結果は膀胱癌の個別化医療に向けての指標となることが期待される。