Figures & data
Figure 1. Immune checkpoint antibodies deplete tumor-specific Tregs in situ. Intratumoral regulatory T cells (Tregs) with tumor-antigen specificity overexpress cytotoxic T lymphocyte associated protein 4 (CTLA-4), and tumor necrosis factor receptor superfamily members OX40 (Tnfsrf4) and GITR (Tnfsrf18) on their surface. Anti-CTLA-4, anti-OX40 and anti-GITR immune checkpoint antibody therapies could deplete intratumoral Tregs by antibody dependent cellular phagocytosis (ADCP) via activating FcgRIV receptors expressed on tumor-associated myeloid cells. This depletion might be insufficient to unleash the anticancer immune response in some tumor contexts. Combinations of immune checkpoint monoclonal antibodies (mAbs) with other immunostimulatory products, such as pattern recognition agonists (PRR), or cytotoxic agents activating myeloid cells and/or immunogenic cell death could potentially dramatically enhance the antitumor immune response. APC, antigen presenting cell; CTL, cytotoxic T lymphocyte; TLR, Toll-like receptor.
