The roles of PD-L1 in the various stages of tumor metastasis

Abstract

The interaction between tumor programmed death ligand 1 (PD-L1) and T-cell programmed cell death 1 (PD-1) has long been acknowledged as a mechanism for evading immune surveillance. Recent studies, however, have unveiled a more nuanced role of tumor-intrinsic PD-L1 in reprograming tumoral phenotypes. Preclinical models emphasize the synchronized effects of both intracellular and extracellular PD-L1 in promoting metastasis, with intricate interactions with the immune system. This review aims to summarize recent findings to elucidate the spatiotemporal heterogeneity of PD-L1 expression and the pro-metastatic roles of PD-L1 in the entire process of tumor metastasis. For example, PD-L1 regulates the epithelial-to-mesenchymal transition (EMT) process, facilitates the survival of circulating tumor cells, and induces the formation of immunosuppressive environments at pre-metastatic niches and metastatic sites. And the complexed and dynamic regulation process of PD-L1 for tumor metastasis is related to the spatiotemporal heterogeneity of PD-L1 expression and functions from tumor primary sites to various metastatic sites. This review extends the current understandings for the roles of PD-L1 in mediating tumor metastasis and provides new insights into therapeutic decisions in clinical practice.

Keywords: EMT; PD-L1; heterogeneity; immune evasion; metastasis.