CBX7 通过抑制 POU2F2 抑制 PD-L1 表达并调节膀胱癌中的免疫反应。
CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer.
机构信息
Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410005, China.
Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China.
出版信息
Biochem Biophys Res Commun. 2022 Jul 12;613:12-18. doi: 10.1016/j.bbrc.2022.04.114. Epub 2022 Apr 28.
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.
膀胱癌（BC）是全球范围内最常见的泌尿系统恶性肿瘤之一。迄今为止，免疫检查点抑制剂（包括 PD-1/PD-L1）已被应用于临床治疗膀胱癌患者，并取得了有前景的效果。进一步提高这些免疫疗法的抗癌效率对膀胱癌至关重要。我们之前关于 CBX7 的 RNA-seq 数据（GSE185630）表明，CBX7 可能抑制癌症中 PD-L1 的表达和 PD-1 检查点途径。在这项研究中，我们揭示了 CBX7 下调 POU2F2 的表达，从而间接抑制 BC 细胞中的 PD-L1。CBX7 的耗竭导致膀胱癌对 PD-1 阻断的耐药性。总的来说，我们的结果表明，CBX7/POU2F2/PD-L1 轴在决定 PD-1 阻断在膀胱癌中的抗肿瘤作用方面起着重要作用。
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