Abstract
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.