CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：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.
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尽管抗PD-L1治疗已用于肾细胞癌（RCC）的临床治疗，但部分患者对其不敏感，这可能归因于PD-L1表达的异质性。在此，我们证明RCC中TOPK（T-LAK细胞起源的蛋白激酶）高表达通过激活ERK2和TGF-β/Smad通路促进PD-L1表达。TOPK与RCC中PD-L1表达水平呈正相关。同时，TOPK显著抑制CD8+ T细胞的浸润和功能，并促进RCC的免疫逃逸。此外，抑制TOPK显著增强CD8+ T细胞浸润，促进CD8+ T细胞活化，增强抗PD-L1治疗效果，并协同增强抗RCC免疫反应。总之，本研究提出了一种新的PD-L1调控机制，有望提高RCC免疫治疗的有效性。
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.
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