ArticleJournal for immunotherapy of cancer2026
VISTA neutralization by immunization reprograms immunosuppression and augments vaccine efficacy in renal carcinoma.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRenal carcinoma remains a highly lethal malignancy, and tumor vaccine efficacy is frequently hampered by a profoundly immunosuppressive tumor microenvironment. V-domain Ig suppressor of T-cell activation (VISTA), an inhibitory immune checkpoint enriched in myeloid cells and regulatory T cells (Tregs), represents a critical barrier to effective antitumor immunity. Targeting VISTA may therefore provide a promising strategy to overcome immune suppression and enhance tumor vaccine efficacy.
methodsRecombinant adenoviral vaccines encoding carbonic anhydrase IX (CAIX) and VISTA (Ad-CAIX and Ad-VISTA) were constructed and validated for efficient antigen expression. The antitumor efficacy of Ad-VISTA/CAIX co-immunization was evaluated in subcutaneous, lung metastatic, orthotopic, and anti-programmed cell death protein 1-resistant renal carcinoma models. Vaccine-induced immune responses were assessed by flow cytometry, immunohistochemistry, ELISA, cell proliferation assays, cytotoxic T lymphocyte (CTL) assays, and in vivo immune cell depletion experiments.
resultsAd-VISTA immunization markedly potentiated the therapeutic efficacy of CAIX-targeted vaccination, resulting in significant tumor growth inhibition and prolonged survival across multiple renal carcinoma models. Mechanistically, VISTA-targeting remodeled the tumor microenvironment by enhancing the infiltration and activation of dendritic cells (DCs) and CD8
conclusionsThese results indicated that vaccine-induced VISTA blockade effectively amplifies DC-mediated CD8
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