TOPK mediates immune evasion of renal cell carcinoma via upregulating the expression of PD-L1.

Although anti-PD-L1 therapy has been used in the clinical treatment of renal cell carcinoma (RCC), a proportion of patients are not sensitive to it, which may be attributed to the heterogeneity of PD-L1 expression. Here, we demonstrated that high TOPK (T-LAK cell-originated Protein Kinase) expression in RCC promoted PD-L1 expression by activating ERK2 and TGF-β/Smad pathways. TOPK was positively correlated with PD-L1 expression levels in RCC. Meanwhile, TOPK significantly inhibited the infiltration and function of CD8 T cells and promoted the immune escape of RCC. Moreover, inhibition of TOPK significantly enhanced CD8 T cell infiltration, promoted CD8 T cell activation, enhanced anti-PD-L1 therapeutic efficacy, and synergistically enhanced anti-RCC immune response. In conclusion, this study proposes a new PD-L1 regulatory mechanism that is expected to improve the effectiveness of immunotherapy for RCC.