The Significance of TGFB1 Expression in Clear Cell Renal Cell Carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15392
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Takahara Taishi 愛知医科大学, 医学部, 助教 (50790317)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腎癌 / TGF-β / 腫瘍微小環境

Outline of Final Research Achievements

To determine whether TGFB1 affects the immune microenvironment of ccRCC, we investigated the association between TGFB1 expression and clinicopathological features using tissue microarray sample from 158 ccRCC and 12 normal kidney tissue. TGFB1 expression was assessed by RNAscope. TGFB1 was significantly upregulated in ccRCC tissue than in normal kidney tissues. Tumors with a high WHO/ISUP grade had higher TGFB1 expression levels. TGFB1-high group displayed significantly shorter relapse-free survival than TGFB1-low group. TGFB1 expression was significantly upregulated in patients who developed distant metastasis after surgery than in patients without metastasis. TGFB1 expression positively correlated with the number of PD-L1-positive cells in the tumor stroma. TGFB1 expression was associated with the formation of tertiary lymphoid structures. Our data provide new insights into the association between tumor biology and tumor microenvironment in ccRCC.

Free Research Field

外科病理　腫瘍免疫　腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、mRNAのin situ hybridizationを用いてccRCC組織におけるTGFB1発現の臨床病理学的意義を報告した最初の研究である。
現在の進行期腎細胞癌の治療においては、PD-L1などを標的とした免疫チェックポイント療法が治療戦略の主体となっているが、今回我々の研究により、腫瘍のTGFB1発現が腫瘍の免疫環境と強い関連があることが示された。我々の研究データはTGF-βを標的とした新たな治療戦略の開発を促進する可能性がある。