Inhibitory immune cells

Inhibitory immune cells are a diverse group of immune cell populations, most notably regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and regulatory B cells (Bregs), that play a critical role in maintaining peripheral tolerance and preventing autoimmunity (Sakaguchi et al., 2008, Cell). These cells exert their suppressive effects through various mechanisms, including the secretion of anti-inflammatory cytokines like IL-10 and TGF-beta, metabolic disruption, and the expression of inhibitory checkpoint molecules such as CTLA-4 and PD-L1 (Vignali et al., 2008, Nature Reviews Immunology). In oncology, the accumulation of these cells within the tumor microenvironment is a major mechanism of therapeutic resistance, as they actively inhibit the anti-tumor activity of effector T cells and natural killer cells (Gabrilovich & Nagaraj, 2009, Nature Reviews Immunology). Consequently, many modern immunotherapies aim to either deplete these populations or neutralize their suppressive signals to enhance the efficacy of the immune system against cancer. Conversely, in the treatment of autoimmune diseases and organ transplantation, the therapeutic goal is often to expand or activate these cells to suppress unwanted immune responses and promote long-term tolerance.

Other names

Immunosuppressive cellsRegulatory immune cellsSuppressor cellsRegulatory T cellsMyeloid-derived suppressor cellsRegulatory B cellsTregsMDSCsBregsM2-polarized macrophages

Therapeutic strategies involve the depletion of immunosuppressive cell populations, inhibition of their recruitment to the tumor microenvironment, or the blockade of inhibitory signaling pathways and metabolic products (e.g., CTLA-4, PD-1, or Arginase-1) that mediate their function.