PD-1 regulation in immune homeostasis and immunotherapy

Harnessing the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis is pivotal in autoimmunity and cancer immunotherapy. PD-1 receptors on immune cells engage with one of its ligands, PD-L1 or PD-L2, expressed on antigen-presenting cells or tumor cells, driving T-cell dysfunction and tumor immune escape. Thus, targeting PD-1/PD-L1 revitalizes cytotoxic T cells for cancer elimination. However, a majority of cancer patients don't respond to PD-1/PD-L1 blockade, and the underlying mechanisms remain partially understood. Recent studies have revealed that PD-1 expression levels or modifications impact the effectiveness of anti-PD-1/PD-L1 treatments. Therefore, understanding the molecular mechanisms governing PD-1 expression and modifications is crucial for innovating therapeutic strategies to enhance the efficacy of PD-1/PD-L1 inhibition. This article presents a comprehensive overview of advancements in PD-1 regulation and highlights their potential in modulating immune homeostasis and cancer immunotherapy, aiming to refine clinical outcomes.