Regulatory T cell immunosuppressive pathways (Treg pathways)

Regulatory T cells (Tregs) are a specialized lineage of CD4+ T cells characterized by the expression of the transcription factor FOXP3, which play a critical role in maintaining immunological self-tolerance and preventing autoimmune diseases (Sakaguchi et al., 2020, Cell). In the tumor microenvironment (TME), Tregs are often recruited and expanded, where they execute potent immunosuppressive functions that hinder anti-tumor immune responses and promote tumor progression (Togashi et al., 2019, Nature Reviews Clinical Oncology). These cells suppress effector T cells and natural killer cells through multiple mechanisms, including the secretion of inhibitory cytokines like TGF-beta and IL-10, the consumption of IL-2 via high-affinity CD25 receptors, and the expression of immune checkpoint molecules such as CTLA-4 and PD-1 (Vignali et al., 2008, Nature Reviews Immunology). Therapeutic targeting of Treg pathways involves strategies to deplete these cells (e.g., via CCR4 or CD25 targeting), inhibit their recruitment to the TME, or block their suppressive signaling molecules to restore the efficacy of cancer immunotherapies. However, systemic disruption of Treg function poses significant safety challenges, primarily the risk of severe immune-related adverse events (irAEs) and the loss of peripheral tolerance leading to multi-organ autoimmunity (Postow et al., 2018, New England Journal of Medicine).

Other names

TregsSuppressor T cellsTreg-mediated immunosuppressionTumor-infiltrating regulatory T cellsTIL-TregsFOXP3+ regulatory T cells

Inhibition of Treg recruitment, depletion of Treg populations via antibody-dependent cellular cytotoxicity (ADCC), and blockade of immunosuppressive effector molecules or receptors such as CTLA-4 and PD-1.