An unexpected role for PD-L1 in front-rear polarization and directional migration

Programmed cell death-ligand 1 (PD-L1)-mediated T cell inhibition through PD-1 is a key checkpoint frequently exploited by tumors to evade immunity. In this issue, Wang et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108083) reveal an unexpected role for PD-L1 in promoting tumor cell front-rear polarity and directionally persistent cell migration, independently of PD-1.