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.
Jinxin Li  1 ,  Huimin Sun  1  2 ,  Meiling Fu  1 ,  Zeyuan Zheng  1 ,  Chunlan Xu  1 ,  Kunao Yang  1 ,  Yankuo Liu  1 ,  Zuodong Xuan  1 ,  Yang Bai  1 ,  Jianzhong Zheng  1 ,  Yue Zhao  1 ,  Zhiyuan Shi  1 ,  Chen Shao  1
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.
PMID: 37404377 DOI: 10.1016/j.isci.2023.107185
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.
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