PD-L1 at the crossroad between RNA metabolism and immunosuppression

Programmed death ligand-1 (PD-L1) is a key component of tumor immunosuppression. The uneven therapeutic results of PD-L1 therapy have stimulated intensive studies to better understand the mechanisms underlying altered PD-L1 expression in cancer cells, and to determine whether, beyond its immune function, PD-L1 might have intracellular functions promoting tumor progression and resistance to treatments. In this Opinion, we focus on paradigmatic examples highlighting the central role of PD-L1 in post-transcriptional regulation, with PD-L1 being both a target and an effector of molecular mechanisms featured prominently in RNA research, such as RNA methylation, phase separation and RNA G-quadruplex structures, in order to highlight vulnerabilities on which future anti-PD-L1 therapies could be built.