V-domain Ig Suppressor of T cell Activation(VISTA)is a negative immune checkpoint that is expressed on multiple immune cell subsets and has been characterized in T cells,macrophages,and myeloid-derived suppressor cell...V-domain Ig Suppressor of T cell Activation(VISTA)is a negative immune checkpoint that is expressed on multiple immune cell subsets and has been characterized in T cells,macrophages,and myeloid-derived suppressor cells.As the only immune checkpoint expressed on naïve T cells,VISTA contributes to the maintenance of T cell quiescence and tolerance.VISTA also regulates multiple myeloid cell activities such as chemotaxis,differentiation,and migration.In the context of cancer,antagonistic monoclonal antibody targeting of VISTA has been shown to aid anti-tumor immunity.Furthermore,combination therapies that include other immune checkpoints such as PD-1 or CTLA-4 with VISTA blockade may enhance therapeutic efficacy in a variety of cancers.Combination therapy may help overcome adaptive resistance to individual checkpoint therapies,thereby improving patient outcomes and survival.Here,we summarize the role of VISTA in myeloid cells and T cells within the tumor microenvironment.We discuss the proposed counter-receptors for VISTA,VISTA antibodies currently in development,and the potential for combination therapies with checkpoint inhibitors such as PD-1 and CTLA-4.展开更多
基金Research was supported by NIH grants R01AR070760 and R01CA214062(Randolph J.Noelle).
文摘V-domain Ig Suppressor of T cell Activation(VISTA)is a negative immune checkpoint that is expressed on multiple immune cell subsets and has been characterized in T cells,macrophages,and myeloid-derived suppressor cells.As the only immune checkpoint expressed on naïve T cells,VISTA contributes to the maintenance of T cell quiescence and tolerance.VISTA also regulates multiple myeloid cell activities such as chemotaxis,differentiation,and migration.In the context of cancer,antagonistic monoclonal antibody targeting of VISTA has been shown to aid anti-tumor immunity.Furthermore,combination therapies that include other immune checkpoints such as PD-1 or CTLA-4 with VISTA blockade may enhance therapeutic efficacy in a variety of cancers.Combination therapy may help overcome adaptive resistance to individual checkpoint therapies,thereby improving patient outcomes and survival.Here,we summarize the role of VISTA in myeloid cells and T cells within the tumor microenvironment.We discuss the proposed counter-receptors for VISTA,VISTA antibodies currently in development,and the potential for combination therapies with checkpoint inhibitors such as PD-1 and CTLA-4.
