Human VISTA/B7-H5 Assay

V-domain Ig suppressor of T cell activation (VISTA) is a recently identified B7 family member that functions as a key negative checkpoint regulator (NCR) to maintain immune homeostasis. Structurally, VISTA is a 55-65 kDa type I transmembrane protein with a single IgV domain, expressed primarily on the surface of hematopoietic cells like myeloid cells (e.g., MDSCs), T cells, and APCs, as well as on some cancer cells. Mechanistically, it inhibits T cell activation and cytokine production, and induces T cell exhaustion to suppress antitumor immunity.

VISTA has been identified in extracellular vesicles, where it resides in intracellular vesicles and is secreted via exosomes. This EV-associated localization allows for rapid mobilization upon immunogenic stimuli and facilitates intercellular communication. By transferring VISTA to target cells, these vesicles may extend the protein’s immunosuppressive reach beyond direct cell-surface interactions, potentially contributing to tumor immune evasion.

Importantly, VISTA is a key marker of endothelial anergy on tumor-associated endothelium, where it prevents T-cell extravasation. It is a promising therapeutic target: first-in-class drugs, including antagonistic monoclonal antibodies (e.g., W0180, TBS-2025), are in early-stage clinical trials for advanced solid tumors, with evidence of manageable safety and dose-dependent pharmacodynamic effects.