Co-stimulatory and inhibitory ligands

Co-stimulatory and inhibitory ligands are a broad class of cell surface proteins that provide the critical secondary signals necessary for the regulation of T-cell-mediated immune responses (Chen & Flies, 2013, Nature Reviews Immunology). These ligands, primarily belonging to the B7 family (e.g., CD80, CD86, PD-L1) and the tumor necrosis factor (TNF) superfamily (e.g., 4-1BBL, OX40L), interact with specific receptors on T-cells to either promote (co-stimulation) or suppress (inhibition) T-cell activation and effector functions (Sharpe & Pauken, 2018, Nature Reviews Immunology). In a physiological state, these pathways maintain a delicate balance between effective immunity against pathogens and the prevention of autoimmunity through self-tolerance. In many cancers, the overexpression of inhibitory ligands like PD-L1 allows tumors to evade immune surveillance by inducing T-cell exhaustion (Janakiram et al., 2016, Immunological Reviews). Conversely, deficiencies in inhibitory signaling or excessive co-stimulation are linked to the development of autoimmune disorders. Pharmacological intervention involves the use of monoclonal antibodies to block inhibitory ligands (checkpoint inhibitors) or the use of decoy receptors and agonists to modulate co-stimulatory pathways, thereby recalibrating the immune response for therapeutic benefit.

Other names

Immune checkpoint ligandsCo-signaling moleculesB7 family ligandsT-cell co-regulatorsCo-stimulatory and co-inhibitory ligands

Blockade of inhibitory ligand-receptor axes or modulation of co-stimulatory ligand availability to regulate T-cell mediated immunity.