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

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

doi:10.1016/j.isci.2023.107185

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

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

Authors

Jinxin Li¹, Huimin Sun^{1

2}, Meiling Fu¹, Zeyuan Zheng¹, Chunlan Xu¹, Kunao Yang¹, Yankuo Liu¹, Zuodong Xuan¹, Yang Bai¹, Jianzhong Zheng¹, Yue Zhao¹, Zhiyuan Shi¹, Chen Shao¹

Affiliations

¹ Department of Urology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.
² Central Laboratory, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.

Abstract

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.

Keywords: Cancer; Immunology; Molecular biology.