Cell Identity and Spatial Distribution of PD-1/PD-L1 Blockade Responders

The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis inhibits T cell activity, impairing anti-tumor immunity. Blocking this axis with therapeutic antibodies is one of the most promising anti-tumor immunotherapies. It has long been recognized that PD-1/PD-L1 blockade reinvigorates exhausted T (T_EX) cells already present in the tumor microenvironment (TME). However, recent advancements in high-throughput gene sequencing and bioinformatic tools have provided researchers with a more granular and dynamic insight into PD-1/PD-L1 blockade-responding cells, extending beyond the TME and T_EX populations. This review provides an update on the cell identity, spatial distribution, and treatment-induced spatiotemporal dynamics of PD-1/PD-L1 blockade responders. It also provides a synopsis of preliminary reports of potential PD-1/PD-L1 blockade responders other than T cells to depict a panoramic picture. Important questions to answer in further studies and the translational and clinical potential of the evolving understandings are also discussed.