Multi-layered control of PD-L1 expression in Epstein-Barr virus-associated gastric cancer.
Multi-layered control of PD-L1 expression in Epstein-Barr virus-associated gastric cancer.
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DOI：
10.20517/2394-4722.2020.12
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Slack FJ
中科院分区：
文献类型：
--
作者：
Miliotis CN;Slack FJ
胃癌(GC)是全球第五大常见癌症。在大约10%的GC病例中，癌细胞显示无处不在的单克隆性EB病毒(EBV)感染。EBV相关性胃癌(EBVaGC)的一个显著特征是高淋巴细胞浸润和免疫检查点蛋白的高表达，其中包括程序性死亡配体1(PD-L1)。这表明EBVaGC是免疫检查点阻断治疗的有力候选者。事实上，最近的几项研究表明，GC中EBV阳性与对程序性细胞死亡蛋白1(PD-1)/PD-L1阻断治疗的阳性反应相关。了解控制EBVaGC中PD-L1表达的机制可以为免疫治疗提供新的预测生物标志物，也可以为联合治疗提供治疗靶点。PD-L1的表达调控涉及多种机制，包括结构变异、转录后调控、内在信号通路的致癌激活以及对外部信号的敏感性增加。本文综述了EBVaGC中PD-L1表达的多层调控的最新进展。
Gastric cancer (GC) is the fifth most common cancer worldwide. In approximately 10% of GC cases, cancer cells show ubiquitous and monoclonal Epstein-Barr virus (EBV) infection. A significant feature of EBV-associated GC (EBVaGC) is high lymphocytic infiltration and high expression of immune checkpoint proteins, including programmed death-ligand 1 (PD-L1). This highlights EBVaGC as a strong candidate for immune checkpoint blockade therapy. Indeed, several recent studies have shown that EBV positivity in GC correlates with positive response to programmed cell death protein 1 (PD-1)/PD-L1 blockade therapy. Understanding the mechanisms that control PD-L1 expression in EBVaGC can indicate new predictive biomarkers for immunotherapy, as well as therapeutic targets for combination therapy. Various mechanisms have been implicated in PD-L1 expression regulation, including structural variations, post-transcriptional control, oncogenic activation of intrinsic signaling pathways, and increased sensitivity to extrinsic signals. This review provides the most recent updates on the multilayered control of PD-L1 expression in EBVaGC.
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