Inhibitory receptor agonists: Emerging strategies in immune modulation

Inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG3, TIM-3, and TIGIT are critical regulators of immune homeostasis, functioning to restrain excessive immune activation and prevent autoimmunity. While the blockade of IRs has transformed cancer immunotherapy by reinvigorating antitumor T cell responses, emerging strategies aim to harness the immunosuppressive potential of these receptors for treating autoimmune and inflammatory diseases. Agonistic antibodies that activate IR signaling have demonstrated promising results in preclinical models by promoting immune tolerance and suppressing pathological effector T cell functions. This review highlights recent progress in the development of agonistic IR-targeted therapies, examining their mechanisms of action, therapeutic efficacy, and the translational challenges that must be addressed to bring these innovative approaches into clinical practice for the management of autoimmunity and inflammatory disorders.