VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy
Open accessAbstract
In the past few years, the field of cancer immunotherapy has made great progress and is finally starting to change the way cancer is treated. We are now learning that multiple negative checkpoint regulators (NCR) restrict the ability of T-cell responses to effectively attack tumors. Releasing these brakes through antibody blockade, first with anti-CTLA4 and now followed by anti-PD1 and anti-PDL1, has emerged as an exciting strategy for cancer treatment. More recently, a new NCR has surfaced called V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA). This NCR is predominantly expressed on hematopoietic cells, and in multiple murine cancer models is found at particularly high levels on myeloid cells that infiltrated the tumors. Preclinical studies with VISTA blockade have shown promising improvement in antitumor T-cell responses, leading to impeded tumor growth and improved survival. Clinical trials support combined anti-PD1 and anti-CTLA4 as safe and effective against late-stage melanoma. In the future, treatment may involve combination therapy to target the multiple cell types and stages at which NCRs, including VISTA, act during adaptive immune responses.
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CD96 inhibits NK cell activity in murine cancer models.
“These include the TIM-3, LAG-3, TIGIT, and B- And T-Lymphocyte-Associated Protein (BTLA) receptors associated with T cell exhaustion as well as VISTA, a receptor found on tumor-infiltrating myeloid cells, whose inhibition promoted anti-tumor immune responses in murine models, and CD96, which has been shown to inhibit NK cell activity in murine cancer models (115–117).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [115]
VISTA inhibition promoted anti-tumor immune responses in murine models.
“These include the TIM-3, LAG-3, TIGIT, and B- And T-Lymphocyte-Associated Protein (BTLA) receptors associated with T cell exhaustion as well as VISTA, a receptor found on tumor-infiltrating myeloid cells, whose inhibition promoted anti-tumor immune responses in murine models, and CD96, which has been shown to inhibit NK cell activity in murine cancer models (115–117).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [115]
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Self-citation
- Authors
- Lines, J. L., Sempere, L. F., Broughton, T., Wang, L., & Noelle, R.
- Affiliations
- Guy's Hospital (GB)
- Dartmouth College (US)
- Corresponding author
- Lines, J. Louise
- Noelle, Randolph
- Venue
- Cancer Immunology Research
- Published
- 2014-06-01
- Volume
- 2
- Issue
- 6
- Pages
- 510-517
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC4085258
- OpenAlex
- W2134644618
- Cited by
- 236
- References
- 72
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 20 · 2023: 21 · 2022: 18 · 2021: 32 · 2020: 29 · 2019: 21 · 2018: 24 · 2017: 21 · 2016: 13 · 2015: 8 · 2014: 3
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (091823)
- Medical Research Council (MR/J006742/1)
- National Cancer Institute (R01CA164225, P30CA023108)
- National Institute of Allergy and Infectious Diseases (R01AI098007)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- VISTA, cancer immunotherapy, immune checkpoint blockade, myeloid cells, tumor-infiltrating myeloid cells, antitumor T-cell responses, anti-PD-1, anti-CTLA-4, combination immunotherapy, melanoma
- MeSH terms
- Animals, Disease Models, Animal, Forecasting, Humans, Immunotherapy, Neoplasms, Precision Medicine, Cell Cycle Checkpoints, B7 Antigens, B7-H1 Antigen, V-Set Domain-Containing T-Cell Activation Inhibitor 1, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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