Figure 2.

The signaling effects of ICRs in antigen-presenting cells. Aside from suppressing T-cell activation, many ICRs regulate the maturation, antigen presentation, cytokine production, and other effector functions of DCs and tumor-associated macrophages. CTLA-4 reduces the surface expression of B7 molecules through trans-endocytosis. LAG-3 and TIGIT trigger signaling in a reverse direction by engaging their respective binding partners MHCII and CD155. On the other hand, PD-1, TIM-3, and VISTA are expressed in APCs and transmit inhibitory signals to inhibit the effector functions of APCs, including phagocytosis, antigen presentation, and cytokine production. Both PD-1 and VISTA are also expressed in tumor-driven MDSCs and contribute to the differentiation and suppressive function of MDSCs.