VISTA: Coming of age as a multi‐lineage immune checkpoint

• Published in: Clinical and experimental immunology 2020-05, Vol.200 (2), p.120-130
• Main Authors: ElTanbouly, M. A., Schaafsma, E., Noelle, R. J., Lines, J. L.
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Antigens; Apoptosis; B7 Antigens - antagonists & inhibitors; B7 Antigens - immunology; Cancer; Cancer immunotherapy; Cell activation; Cell death; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; Cytotoxicity; Gene Expression Regulation, Neoplastic - immunology; Humans; Immune checkpoint; Immunity, Innate; Immunoregulation; Immunotherapy; Lymphocytes T; Metastases; Myeloid cells; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - immunology; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; PD-1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Review; VISTA
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13415

Summary The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co‐stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti‐tumor immunity. The ideal cancer immunotherapy treatment will improve both cross‐priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD‐1) and cytotoxic T lymphocyte antigen 4 (CTLA‐4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V‐set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non‐redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy. VISTA is an immunoregulatory protein with an important nonredundant role in maintaining immune homeostasis. VISTA is expressed in numerous human cancers and correlates with poor clinical responses. Antibody‐mediated VISTA blockade has shown promise in multiple tumor models, synergizing with the blockade of other inhibitory checkpoints.