Figure 2.

Overview of the immunosuppressive mechanisms of tumor-associated macrophages (TAMs). TAMs express an array of effector molecules that inhibit antitumor immune responses; this includes cell surface receptors, cytokines, chemokines, and enzymes. Inhibition of immune responses by direct cell-to cell-contact is based on the interaction of TAM receptor ligands with their counterpart death and/or inhibitory receptors expressed by the target effector cells. TAMs express the ligand receptors for PD-1 and CTLA-4 that upon activation suppress cytotoxic functions of T cell, natural killer (NK) T cells, and NK cells. TAMs also express the ligand for the death receptors FAS and TRAIL that triggers caspase-dependent cell death (apoptosis) in target cells. TAMs also express the nonclassical HLA-G that inhibits T cell function through interaction with the costimulatory signal of T cells ILT2 and HLA-E that inhibit NK cells through CD94 (also known as NKG2). TAMs secrete the cytokines IL-10 and TGF-β that inhibit T cell effector functions and induce regulatory functions and chemokines CCL5, CCL20, and CCL22 that recruit nT_reg cells. TAMs secrete Arginase I that inhibit TCR ζ chain re-expression inactivated T cells by the depletion of L-arginine. (Adapted from Noy and Pollard (2014).³⁶ Copyright 2014 Elsevier.)