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

Abstract

Abstract 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 (TEX) 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 TEX 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.

Keywords

• cancer
• immunotherapy
• PD‐1/PD‐L1 blockades
• T‐cell exhaustion
• stem‐like T‐cells
• cell therapy