Abstract
VISTA is an up-and-coming immune checkpoint molecule that can become the target of new cancer immunotherapy treatments. Immune cells in the tumor microenvironment can largely influence the progression of cancer through inhibitory and stimulatory pathways. Indeed, VISTA is expressed on many immune cells, including T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. VISTA has predominantly been shown to act in an immune-suppressing manner that enables cancer progression. This review will delve into results from preclinical murine studies of anti-VISTA monoclonal antibody treatments, bring together recent studies that detect VISTA expression on immune cells from patient tumors of various cancers, and discuss ongoing clinical trials involving VISTA.
Highlights
TO VISTAV-domain Ig suppressor of T cell activation (VISTA)V-domain Ig suppressor of T cell activation (VISTA) has been identified in mice as an Ig superfamily inhibitory ligand with an extracellular domain bearing homology to PD-L1, a B7 family ligand (6)
These findings come from studies of the interaction between THP-1 acute myeloid leukemia cells that heavily secrete galectin-9 and soluble VISTA, and Jurkat T cells, which highly express VISTA, so further research is needed to determine if the reported ligand-receptor interaction applies in a broader context
A study on hepatocellular carcinoma (HCC) shows that tumor cell expression of VISTA correlates with prolonged overall survival, and another on high grade serous ovarian carcinoma (HGSOC) shows that tumor cell expression of VISTA is associated with prolonged progression-free survival (45, 46)
Summary
Immune checkpoint molecules regulate the immune system’s inhibitory and stimulatory pathways in order to maintain homeostasis. Blocking the inhibitory checkpoint molecules can unleash the immune cells to proliferate better and fight against tumor cells With this knowledge, immune checkpoint therapy is a growing form of treatment for an increasing number of cancer types. Immune checkpoint therapy is a growing form of treatment for an increasing number of cancer types Both CTLA-4 and PD-1 are inhibitory checkpoint molecules that limit activated T cells from their effector functions. The first immune checkpoint therapies to be developed were antibodies against CTLA-4 and, subsequently, antibodies against PD-1 (1) These treatments were gamechanging by durably increasing cancer patients’ survival rates, but such benefits only applied to a fraction of patients and did not extend to all cancer types (2). To understand how VISTA blockade can benefit patients as a cancer immune checkpoint therapy, we must analyze which cells express VISTA in the tumor microenvironment and the consequences of the expression
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