Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) (CTLA-4, PD-1)

Immune checkpoint blockade refers to the inhibition of negative regulatory pathways that suppress T lymphocyte activity. The most clinically relevant targets are Cytotoxic T‑lymphocyte-associated protein 4 (CTLA‑4) and Programmed cell death protein 1 (PD‑1), both expressed on activated T cells. These receptors normally function to maintain self-tolerance and prevent overactivation of the immune system by delivering inhibitory signals upon binding their ligands on antigen-presenting cells. In cancer therapy, monoclonal antibodies block these checkpoints—releasing the brakes on cytotoxic CD8+ T lymphocytes—thereby promoting anti-tumor immunity. This approach has revolutionized treatment for several cancers but is associated with unique patterns of resistance as well as significant risks for autoimmune toxicity[1][2].

Other names

Immune checkpoint moleculesImmune checkpointsCD152 (for CTLA-4)CD279 (for PD-1)

Drugs targeting these molecules act by blocking inhibitory signals delivered by CTLA‑4 or PD‑1 to T cells, thereby enhancing T cell activation and proliferation against tumor cells[1][2].