ArticleExperimental hematology & oncology2024
VISTA drives macrophages towards a pro-tumoral phenotype that promotes cancer cell phagocytosis yet down-regulates T cell responses.
Article in Experimental hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- VISTA as a myeloid-centered checkpoint axis in cancer: biology, tumor microenvironment, and therapeutic implications.Medical oncology (Northwood, London, England) · 2026Review
- Roles of V-domain Ig suppressor of T-cell activation-mediated immunoregulation in tumor immune escape (Review).Oncology letters · 2026Review
- Cuprotosis-related gene subtypes, prognostic modeling, and tumor microenvironment remodeling in breast cancer.Translational cancer research · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
- Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.Molecular and cellular biochemistry · 2026Review
- Spike protein-induced VSIR-ISX signaling disrupts metabolic homeostasis and promotes COVID-19-related immune dysfunction.Cell biology and toxicology · 2025Article
- Keratinocyte VISTA attenuates UV light-induced skin injury by suppressing cutaneous type I interferon (IFN-I) response.bioRxiv : the preprint server for biology · 2025Article
- The impact of the tumor microenvironment on macrophages.Frontiers in immunology · 2025Review
- Roles of tumor-associated macrophages in triple-negative breast cancer progression.Frontiers in immunology · 2025Review
- Eliminating a barrier: Aiming at VISTA, reversing MDSC-mediated T cell suppression in the tumor microenvironment.Heliyon · 2024Review
- How lactate affects immune strategies in lymphoma.Frontiers in molecular biosciences · 2024Review
- VISTA in hematological malignancies: a review of the literature.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundVISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation.
methodsMacrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34
resultsEctopic expression of VISTA in the monocytic model cell line THP-1 or in primary monocytes triggered differentiation towards the macrophage lineage, with a marked increase in M2-like macrophage-related gene expression and decrease in M1-like macrophage-related gene expression. VISTA expression in THP-1 and monocyte-derived macrophages strongly downregulated expression of SIRPα, a prominent 'don't eat me' signal, and augmented phagocytic activity of macrophages against cancer cells. Intriguingly, expression of VISTA's extracellular domain alone sufficed to trigger phagocytosis in ∼ 50% of cell lines, with those cell lines also directly binding to recombinant human VISTA, indicating ligand-dependent and -independent mechanisms. Endogenous VISTA expression was predominantly higher in M2-like macrophages compared to M0- or M1-like macrophages, with a positive correlation observed between VISTA expression in M2c macrophages and their phagocytic activity. VISTA-expressing macrophages demonstrated a unique cytokine profile, characterized by reduced IL-1β and elevated IL-10 secretion. Furthermore, VISTA interacted with MHC-I and downregulated its surface expression, leading to diminished T cell activation. Notably, VISTA surface expression was identified in monocytes from all lymphoma patients but was less prevalent in healthy donors.
conclusionsCollectively, VISTA expression associates with and drives M2-like activation of macrophages with a high phagocytic capacity yet a decrease in antigen presentation capability to T cells. Therefore, VISTA is a negative immune checkpoint regulator in macrophage-mediated immune suppression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.