fig2

Figure 2. The proposed effects of VISTA blockade in the TME. The administration of an anti-VISTA antagonist results in the recruitment of T cells to the TME, as well as a reduction in chemotaxis of MDSCs and macrophages into the TME. VISTA antagonism also results in decreased differentiation of MDSCs into TAMS is also decreased; reduced production of suppressive cytokines by MDSCs and macrophages, resulting in decreased T cell inhibition, and increased production of IFNγ and IL-2. DCs become more activated and upregulate Erk1/2 and Jnk1/2, potentially regulating the IL-23/IL-17 inflammatory axis. Neutrophil and PMN-MDSC levels are decreased in the TME by the reduction of chemotaxis after VISTA blockade. Altogether, these effects of VISTA antagonism result in reduced tumor burden. VISTA: V-domain Ig Suppressor of T cell Activation; TME: tumor microenvironment; MDSCs: myeloid-derived suppressor cells; TAMS: tumor associated macrophages.