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

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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.

Graphical abstract

Highlights

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High expression of TOPK in renal cell carcinoma predicts poor prognosis
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Activation of TOPK promotes PD-L1-mediated immune escape in renal cell carcinoma
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The presence of TOPK is required for the TGF-β/Smad pathway to function
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TOPK inhibition offers new ideas for renal cell carcinoma treatment

Abstract

Molecular biology; Immunology; Cancer

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Author and article information

Contributors

Chen Shao

Journal

Journal ID (nlm-ta): iScience

Journal ID (iso-abbrev): iScience

Title: iScience

Publisher: Elsevier

ISSN (Electronic): 2589-0042

Publication date PMC-release: 20 June 2023

Publication date Collection: 21 July 2023

Publication date (Electronic): 20 June 2023

Volume: 26

Issue: 7

Electronic Location Identifier: 107185

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

Author notes

[∗ ]Corresponding author cshao@ 123456xah.xmu.edu.cn

[3]

These authors contributed equally

[4]

Lead contact

Article

Publisher Item ID: S2589-0042(23)01262-2 Publisher ID: 107185

DOI: 10.1016/j.isci.2023.107185

PMC ID: 10316654

SO-VID: e0a7a6ca-056a-435c-a04f-e4e3a0250c5e

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 26 March 2023

Date revision received : 8 May 2023

Date accepted : 16 June 2023

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