Regulation of Tumor Dendritic Cells by Programmed Cell Death 1 Pathways

The advent of immune checkpoint blockade therapy has revolutionized cancer treatments and is partly responsible for the significant decline in cancer-related mortality observed during the last decade. Immune checkpoint inhibitors, such as anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1), have demonstrated remarkable clinical successes in a subset of cancer patients. However, a considerable proportion of patients remain refractory to immune checkpoint blockade, prompting the exploration of mechanisms of treatment resistance. Whereas much emphasis has been placed on the role of PD-L1 and PD-1 in regulating the activity of tumor-infiltrating T cells, recent studies have now shown that this immunoregulatory axis also directly regulates myeloid cell activity in the tumor microenvironment including tumor-infiltrating dendritic cells. In this review, I discuss the most recent advances in the understanding of how PD-1, PD-L1, and programmed cell death ligand 2 regulate the function of tumor-infiltrating dendritic cells, emphasizing the need for further mechanistic studies that could facilitate the development of novel combination immunotherapies for improved cancer patient benefit. The Journal of Immunology, , 2024, 212: 1397-1405.