Immune costimulatory receptor

Immune costimulatory receptors are a diverse group of cell surface proteins that provide the necessary secondary signals for the full activation, proliferation, and survival of T cells upon engagement with an antigen-presenting cell (Chen & Flies, 2013, Nature Reviews Immunology). These receptors are broadly categorized into the Immunoglobulin (Ig) superfamily, such as CD28 and Inducible T-cell Costimulator (ICOS), and the Tumor Necrosis Factor Receptor (TNFR) superfamily, including 4-1BB (CD137), OX40 (CD134), and GITR (Sharpe, 2009, Immunological Reviews). Their primary biological function is to modulate the intensity and duration of the immune response, ensuring effective clearance of pathogens while preventing autoimmunity (Croft, 2009, Nature Reviews Immunology). In the context of disease, these receptors are major therapeutic targets; agonists are being developed to stimulate anti-tumor immunity in cancer patients, while antagonists or decoy receptors are used to treat autoimmune diseases and prevent organ transplant rejection (Mellman et al., 2011, Nature). However, therapeutic manipulation of these pathways carries risks, such as excessive cytokine production or off-target immune attacks on healthy tissues, necessitating careful dose titration and biomarker monitoring (Weber et al., 2015, Journal of Clinical Oncology).

Other names

Costimulatory moleculesT-cell costimulatory receptorsPositive immune checkpointsCo-stimulatory receptors

Agonism of costimulatory receptors to enhance T-cell effector function and proliferation in oncology, or inhibition of costimulatory pathways (often via ligand blockade) to induce immunosuppression in autoimmune disorders and transplantation (Chen & Flies, 2013; Sharpe, 2009).