The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1. Activation of common oncogenic pathways such as JAK/STAT, RAS/ERK, or PI3K/AKT/MTOR, as well as treatment with cytotoxic agents have also been shown to affect tumoral PD-L1 expression. Correlative studies of clinical trials with PD-1/PD-L1 inhibitors have so far shown markedly discordant results regarding the value of PD-L1 expression as a marker of response to treatment. As the indications for immune checkpoint inhibition broaden, understanding the regulation of PD-L1 in cancer will be of utmost importance for defining its role as predictive marker but also for optimizing strategies for cancer immunotherapy. Here, we review the current knowledge of PD-L1 regulation, and its use as biomarker and as therapeutic target in cancer.

中文翻译：

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癌症中程序性死亡蛋白配体 1 的遗传、转录和翻译后调节：生物学和临床相关性。

程序性死亡蛋白 1 (PD-1) 及其配体 (PD-L1) 代表了癌症中一个明确表征的免疫检查点，被批准用于常规临床使用的单克隆抗体有效靶向。PD-L1 表达的调节很复杂，不同肿瘤类型之间存在差异，并且发生在遗传、转录和转录后水平。据报道，在几种肿瘤类型中，PD-L1 基因座的拷贝数改变的频率各不相同。在转录水平，许多转录因子似乎调节 PD-L1 表达，包括 HIF-1、STAT3、NF-κB 和 AP-1。常见致癌途径（如 JAK/STAT、RAS/ERK 或 PI3K/AKT/MTOR）的激活以及细胞毒性药物治疗也被证明会影响肿瘤 PD-L1 的表达。迄今为止，PD-1/PD-L1抑制剂临床试验的相关研究显示，关于PD-L1表达作为治疗反应标志物的价值，结果明显不一致。随着免疫检查点抑制适应症的扩大，了解 PD-L1 在癌症中的调节对于确定其作为预测标记物的作用以及优化癌症免疫治疗策略至关重要。在这里，我们回顾了 PD-L1 调节的当前知识，及其作为癌症生物标志物和治疗靶点的用途。