ARHGAP11A Is a Novel Prognostic and Predictive Biomarker Correlated with Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor and immune dysfunction is associated with ccRCC poor prognosis. The RhoGTPase-activating proteins (RhoGAPs) family was reported to affect ccRCC development, but its role in immunity and prognosis prediction for ccRCC remain unknown. In the current study, we found was the only independent risk factor among 33 RhoGAPs (hazard ratio [HR] 1.949, 95% confidence interval [CI] 1.364-2.785). High level was associated with shorter overall survival (OS, HR 2.040, 95% CI 1.646-3.417) and is a prognostic biomarker for ccRCC. knockdown suppressed renal cell carcinoma (RCC) cell proliferation, colony formation, and migration, suggesting the promoting role of on RCC development. Mechanistically, might contribute to the suppressive tumor immune microenvironment (TIME). High level was correlated with infiltration of immunosuppressive cells (including T helper 2 (Th2) cells, regulatory T (Treg) cells, myeloid derived suppressor cells (MDSC), and M2 macrophage cells), activation of immunosuppressive pathways (IL6-JAK-STAT3 signaling and IFNγ response), and expression of inhibitory immune checkpoints (ICs). could promote T cell exhaustion and induce immune escape. ccRCC patients with low level were more suitable for immune checkpoint inhibitors (ICIs) therapy, while those with high level might benefit from a combination of blockade and ICIs. In all, might serve as a novel prognostic marker, therapeutic target, and predictor in the clinical response to ICIs therapy for ccRCC.