TOPK通过上调PD-L1的表达介导肾细胞癌的免疫逃逸。

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

作者信息

Li Jinxin, Sun Huimin, Fu Meiling, Zheng Zeyuan, Xu Chunlan, Yang Kunao, Liu Yankuo, Xuan Zuodong, Bai Yang, Zheng Jianzhong, Zhao Yue, Shi Zhiyuan, Shao Chen

机构信息

Department of Urology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.

Central Laboratory, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.

出版信息

iScience. 2023 Jun 20;26(7):107185. doi: 10.1016/j.isci.2023.107185. eCollection 2023 Jul 21.

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.