PDCD1 (programmed cell death protein 1) is a gene encoding the PD-1 receptor, an immune checkpoint protein expressed on activated T cells, B cells, and myeloid cells. As a key regulator of immune tolerance, PD-1 interacts with its ligands PD-L1 and PD-L2 to inhibit T-cell activation, preventing excessive immune responses and autoimmune damage. However, many cancers exploit this pathway by overexpressing PD-L1 to suppress antitumor immunity, enabling immune evasion.
PDCD1-targeted antibodies, known as PD-1 inhibitors, block this interaction, restoring T-cell-mediated tumor destruction. Developed as part of immune checkpoint inhibitor therapies, these antibodies (e.g., nivolumab, pembrolizumab) have revolutionized cancer treatment. Approved for melanoma, lung cancer, and other malignancies, they demonstrate durable responses in subsets of patients. Their efficacy correlates with tumor PD-L1 expression and mutational burden, though responses vary widely.
Research continues to optimize PD-1 blockade through combination strategies (e.g., with CTLA-4 inhibitors or chemotherapy) and biomarker-driven patient selection. Challenges include managing immune-related adverse events and overcoming resistance mechanisms. As a cornerstone of immuno-oncology, PDCD1 antibodies exemplify the shift toward harnessing innate immunity against cancer, offering hope for previously untreatable cancers.