A novel negative checkpoint regulator designated V-domain Ig Suppressor of T cell Activation (VISTA) is a newly identified Ig domain-containing immune-checkpoint molecule that directly suppresses T-cell activation in vitro and in vivo. The human and murine VISTA / B7-H5 / GI24 proteins share 90% identity and display similar expression patterns. VISTA / B7-H5 / GI24 is constitutively expressed within the hematopoietic compartment, with the highest expression level on myeloid cells and a lower level on CD4+, CD8+ T cells, and Foxp3+CD4+ regulatory T cells. A soluble VISTA-Ig protein that contains the extracellular domain fused with Ig-crystalizable fragment (Fc) or full-length VISTA / B7-H5 / GI24 expressed on APCs acts as a ligand to suppress T-cell proliferation and cytokine production. In addition, VISTA / B7-H5 / GI24 might function as an inhibitory receptor on T cells to suppress their activation . VISTA / B7-H5 / GI24-specific monoclonal antibody (mAb) enhances disease severity in the experimental autoimmune encephalomyelitis (EAE) model, as well as boosts antitumor immunity in multiple murine tumor models.
Kathleen M. Mahoney et al. Combination cancer immunotherapy and new immunomodulatory targets. Nature Reviews Drug Discovery 2015;14:561–584.
|Co-inhibitory immune checkpoint pathways||Co-stimulatory immune checkpoint pathways|
|PD1 & PD-L1 immune checkpoint pathway||CD40 & CD40L immune checkpoint pathway|
|CTLA-4 & CD80 (CD86) immune checkpoint pathway||OX40 & OX40L immune checkpoint pathway|
|B7-H3 / CD276 immune checkpoint pathway||HVEM & LIGHT immune checkpoint pathway|
|B7-H4 / B7S1 / B7x immune checkpoint pathway||CD28 & CD80 (CD86) immune checkpoint pathway|
|HVEM & BTLA immune checkpoint pathway||GITR & GITR Ligand immune checkpoint pathway|
|HVEM & CD160 immune checkpoint pathway||CD27 & CD70 immune checkpoint pathway|
|LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway||4-1BB & 4-1BBL immune checkpoint pathway|
|Galectin-9 & TIM-3 immune checkpoint pathway||ICOS & ICOS Ligand immune checkpoint pathway|
|Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway||CD266 & CD155 immune checkpoint pathway|
|CEACAM1 / CD66a immune checkpoint pathway|
|SIRP alpha & CD47 immune checkpoint pathway|
|2B4 & CD48 immune checkpoint pathway|
|TIGIT & CD155 immune checkpoint pathway|