MP18-03 TUMOR-INFILTRATING CD39+CD8+ T CELLS DETERMINE POOR PROGNOSIS AND IMMUNE EVASION IN CLEAR-CELL RENAL CELL CARCINOMA PATIENTS

Abstract

INTRODUCTION AND OBJECTIVE: Tumor microenvironment is important in the progression of Clear cell renal cell carcinoma (ccRCC) and its prognostic value is still unclear. Recent reports demonstrated Tumor-infiltrating CD39+CD8+ T cells are abundant, but their function remains obscure.In this study, we want to assess clinical value of CD39+CD8+ T cells and seek a potential therapeutic target in ccRCC METHODS: Two Zhongshan Hospital cohorts (ZSHC) contained 243 non-metastatic ccRCC patients who underwent nephrectomy and 85 metastatic ccRCC patients treated by tyrosine kinase inhibitors (TKIs). In vitro, fresh tumor tissues from another 48 ccRCC patients were used to assess the potential therapeutic worth of the CD39 inhibitor. Immune cell functions were analyzed by flow cytometry. Kaplan–Meier analysis and COX regression model were applied for survival analyses RESULTS: We found that accumulation of CD39+CD8+ T cells indicated poor prognosis (p<0.0001). But high CD39+CD8+ T cells indicated therapeutic benefit of TKIs therapy (p=0.015). CD39+CD8+ T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39+CD8+ T cells and Tregs (p=0.037) and M2-polarized macrophages (p<0.0001). Finally, inhibition of CD39 partially restores the antitumor function of CD8+ T cells. Study limitation includes the unclear impacts of CD39 in vivo. CONCLUSIONS: High CD39+CD8+ T cells indicated poor prognosis in ccRCC, due to impaired antitumor function of CD39+CD8+ T cells. Thus, CD39 is a promising target for immunotherapy in ccRCCSource of Funding: This study was funded by grants from National Natural Science Foundation of China (81671628, 31770851, 81702496, 81702497, 81702805, 81772696, 81871306, 81872082), Shanghai Municipal Natural Science Foundation (16ZR1406500), Guide Project of Science and Technology Commission of Shanghai Municipality (17411963100), Shanghai Sailing Program (18YF1404500, 19YF1407900, 19YF1427200), Shanghai Municipal Commission of Health and Family Planning Program (20174Y0042, 201840168, 20184Y0151), Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation (YJYQ201802) and Shanghai Cancer Research Charity Center. All these study sponsors have no roles in the study design, in the collection, analysis and interpretation of data.