VSIG-8 is a co-inhibitory ligand and an immune checkpoint molecule for human T cells

Abstract Cell surface-localized and secreted immunoglobulin superfamily (IgSF) proteins play central roles in regulating adaptive and innate immune responses, and are primary targets for the development of new immunotherapeutics. In this work we provide biologic-functional insight for VISG-8, one member of this important class of proteins. VSIG-8 inhibits the production of cytokines (IL-2, IFN-gamma, IL-17, IL-6, and IL-19), chemokines (MCP-1, MCP-10, and IP-10) and other proteins (IGFBP3 and RBP4) on anti-CD3 activated human CD3 T cells. Furthermore, VSIG-8 significantly reduces the production of IFN-gamma and IL-2 on both CD4 and CD8 T cells in the presence of T-cell receptor signaling. In addition, VSIG-8 markedly suppresses anti-CD3-induced human T cell proliferation. Moreover, VSIG-8 profoundly decreases the conversion of naïve CD4+ T cells into Th1 cells. Thus, we have identified VSIG-8 as a new immune checkpoint molecule that is able to inhibit human T-cell activation. This novel human T-cell co-inhibitory ligand may be a unique target for developing new immunotherapy strategies for the treatment of human cancers, autoimmune disorders, and infection diseases.