Inhibitory cytokines

The target "Effector T cells and APCs via inhibitory cytokines" refers to the immunosuppressive signaling network mediated by cytokines such as Interleukin-10 (IL-10), Transforming Growth Factor-beta (TGF-beta), and Interleukin-35 (IL-35) (Vignali et al., 2008, Nature Reviews Immunology). These molecules are primarily secreted by regulatory T cells (Tregs) and other suppressor cells to maintain peripheral tolerance and prevent autoimmunity. They function by directly inhibiting the activation, proliferation, and effector functions of CD4+ and CD8+ T cells, while also modulating antigen-presenting cells (APCs) to reduce their capacity for T cell stimulation (Shevach, 2009, Immunity). In oncology, this pathway is frequently exploited by tumors to evade the host immune system, making it a significant focus for checkpoint inhibition and combination therapies (Batlle and Massagué, 2019, Immunity). Conversely, enhancing this pathway is a therapeutic goal in treating chronic inflammatory and autoimmune disorders (Saraiva and O'Garra, 2010, Nature Reviews Immunology). Drugs interacting with this axis include cytokine mimetics like Pegilodecakin and various TGF-beta inhibitors such as Galunisertib and Bintrafusp alfa.

Other names

Immunosuppressive cytokinesRegulatory cytokinesTreg-mediated suppressionIL-10 and TGF-beta signaling axis

Therapeutic agents either act as agonists to enhance inhibitory cytokine signaling for the treatment of autoimmune diseases or as antagonists (antibodies, small molecules, or traps) to block these signals and restore anti-tumor immunity in cancer patients (Batlle and Massagué, 2019, Immunity).