Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
Int J Mol Sci. 2021 May 20;22(10):5383. doi: 10.3390/ijms22105383.
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has long been implicated in modeling antitumor immunity; PD-1/PD-L1 axis inhibitors exert their antitumor effects by relieving PD-L1-mediated suppression on tumor-infiltrating T lymphocytes. However, recent studies have unveiled a distinct, tumor-intrinsic, potential role for PD-L1. In this review, we focus on tumor-intrinsic PD-L1 signaling and delve into preclinical evidence linking PD-L1 protein expression with features of epithelial-to-mesenchymal transition program, cancer stemness and known oncogenic pathways. We further summarize data from studies supporting the prognostic significance of PD-L1 in different tumor types. We show that PD-L1 may indeed have oncogenic potential and act as a regulator of tumor progression and metastasis.
程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）免疫检查点长期以来一直被认为与抗肿瘤免疫有关；PD-1/PD-L1 轴抑制剂通过缓解 PD-L1 介导的对肿瘤浸润性 T 淋巴细胞的抑制作用发挥其抗肿瘤作用。然而，最近的研究揭示了 PD-L1 的一个独特的、内在的肿瘤内在的潜在作用。在这篇综述中，我们重点介绍内在的 PD-L1 信号，并深入研究将 PD-L1 蛋白表达与上皮-间充质转化程序、癌症干性和已知致癌途径的特征联系起来的临床前证据。我们进一步总结了支持 PD-L1 在不同肿瘤类型中具有预后意义的数据。我们表明，PD-L1 确实可能具有致癌潜力，并作为肿瘤进展和转移的调节剂。
