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

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

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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