Figure 2.

Antibody checkpoint intrinsic and extrinsic signaling. (A) Intrinsic signaling. Antibody checkpoints relay aggregated antibody Fc-induced signals into effector cells (MΦ) in a concerted manner through ITAM containing activating (aFcγR) and ITIM-containing inhibitory (iFcγR) Fc gamma receptors. FcγR-expressing cell responses include phagocytosis, immune complex endocytosis, and antigen presentation. (B) Extrinsic signaling. Antibody checkpoints promote clustering and signaling induced by antibody targeted receptors in an antibody Fv and Fc co-dependent manner. Cellular responses are determined by the antibody-targeted receptor's function e.g., macrophage co-stimulation or tumor cell apoptosis.