4.7 Article

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

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ISCIENCE
卷 26, 期 7, 页码 -

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CELL PRESS
DOI: 10.1016/j.isci.2023.107185

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This study demonstrates that high expression of TOPK in RCC promotes PD-L1 expression by activating ERK2 and TGF-beta/Smad pathways. TOPK is also shown to inhibit CD8(+) T cell infiltration and function, promoting immune escape in RCC. Inhibition of TOPK enhances CD8(+) T cell infiltration, activation, anti-PD-L1 therapeutic efficacy, and synergistically enhances anti-RCC immune response.
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-beta/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.

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