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

Programmed cell death protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are critical inhibitory receptors expressed on T cells that function as immune checkpoints to maintain self-tolerance and prevent autoimmunity [1, 11]. In the context of oncology, tumors often exploit these pathways to evade immune detection and destruction [8, 9]. CTLA-4 primarily regulates the early stages of T-cell activation (priming) within the lymph nodes by competing with the co-stimulatory receptor CD28 for binding to B7 ligands on antigen-presenting cells [4, 5]. In contrast, PD-1 acts during the later effector phase within peripheral tissues and the tumor microenvironment, where it binds to its ligands (PD-L1 and PD-L2) to suppress T-cell activity [6, 7]. Therapeutic blockade of these receptors using monoclonal antibodies, such as nivolumab and ipilimumab, releases the brakes on the immune system, enabling a robust anti-tumor response [1, 13]. Dual blockade of both PD-1 and CTLA-4 has shown synergistic efficacy in various cancers, including melanoma and lung cancer, although it is associated with a higher incidence of immune-related adverse events compared to monotherapy [2, 3, 15].

Other names

CD279PDCD1CD152CTLA4Immune checkpointsPD-1/CTLA-4 axis

Blockade of inhibitory T-cell signaling pathways to restore anti-tumor immunity; CTLA-4 inhibition enhances T-cell priming in lymph nodes, while PD-1 inhibition restores effector function in the tumor microenvironment [1, 4, 7].