CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer

CBX7 抑制 POU2F2 以抑制 PD-L1 表达并调节膀胱癌的免疫反应

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作者:Weigang Ren, Jiannan Ren, Naiwen Zhang, Xinlin Liu, Yao Deng, Yanyan Jiang, Bin Yan, Xiaoxiong Xiao, Haixin Yu

Abstract

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system worldwide. To date, immune checkpoint inhibitors (including PD-1/PD-L1) have been applied to treat patients with bladder cancer in the clinic and achieved the promising outcome. Further improvement of the anticancer efficiency of these immune therapies is crucial for bladder cancer. Our previous RNA-seq data on CBX7 (GSE185630) suggested that CBX7 might repress PD-L1 expression and PD-1 checkpoint pathway in cancer. In this study, we revealed that CBX7 downregulated the expression of POU2F2 that indirectly repressed the PD-L1 in BC cells. Depletion of CBX7 resulted in resistance to PD-1 blockade in bladder cancer. Collectively, our results suggested that the CBX7/POU2F2/PD-L1 axis plays an important role in determining the antitumor effect of PD-1 blockade in bladder cancer.

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