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

iScience (Jul 2023)

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

Affiliations

Jinxin Li: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Huimin Sun: 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
Meiling Fu: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Zeyuan Zheng: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Chunlan Xu: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Kunao Yang: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Yankuo Liu: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Zuodong Xuan: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Yang Bai: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Jianzhong Zheng: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Yue Zhao: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Zhiyuan Shi: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China
Chen Shao: Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China; Corresponding author

Journal volume & issue: Vol. 26, no. 7
p. 107185

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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