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VISTA / GI24 is a transmembrane protein expressed in bone, on embryonic stem cells (ESCs), and on tumor cell surfaces. On ESC s, Gi24 appears to positively interact with BMP-4, potentiating BMP signaling and the transition from an undifferentiated to a differentiated state. On tumor cells, Gi24 both promotes MT1-MMP expression and activity and serves as a substrate for MT1-MMP. This increases the potential for cell motility. Mature human Gi24 contains a 162aa extracellular region with one V-type Ig-like domain and a 96aa cytoplasmic domain. Human Gi24 undergoes proteolytic cleavage by MT1-MMP, generating a soluble 30kDa extracellular fragment plus a 25-30kDa membrane-bound fragment. VISTA is a negative checkpoint regulator and is expressed on myeloid cells, T-cells and human TILs (tumor infiltrating lymphocytes) on MDSCs (myeloid-derived suppressor cells) in the TME (tumor microenvironment). It is very likely both a ligand and receptor and is a promising target for cancer immunotherapy.
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