ArticleJournal for immunotherapy of cancer2026
LGALS9 blockade augments vaccine-induced immune responses against prostate cancer.
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
backgroundProstate-specific membrane antigen (PSMA)-based vaccination represents a promising immunotherapeutic strategy for prostate cancer; however, its efficacy remains constrained by tumor-induced immune evasion and insufficient activation of antigen-presenting cells. Galectin-9 (LGALS9), an immunoregulatory lectin that contributes to immune suppression, is therefore an attractive target for overcoming tumor-induced immune tolerance.
methodsRecombinant adenoviral vaccines encoding PSMA and LGALS9 (Ad-PSMA and Ad-LGALS9) were generated and validated for antigen expression in vitro and in vivo. Therapeutic efficacy was evaluated in murine subcutaneous, bone metastatic, and humanized prostate cancer models. Vaccine-induced immune responses were characterized by flow cytometry, ELISA, enzyme-linked immunospot (ELISpot), immunohistochemistry, EdU proliferation assays, cytotoxic T lymphocyte assays, and cell depletion experiments.
resultsPre-immunization with Ad-LGALS9 significantly potentiated the therapeutic efficacy of the Ad-PSMA vaccine in subcutaneous, bone metastatic, and humanized prostate cancer models, resulting in pronounced tumor growth inhibition and prolonged survival. Mechanistically, LGALS9 targeting enhanced dendritic cell (DC) activation and maturation, upregulating CD80, CD86, major histocompatibility complex-II, and CD40 expression and promoting efficient antigen cross-presentation. This facilitated robust priming and expansion of multifunctional CD8
conclusionsTargeting LGALS9 enhances DC-mediated CD8
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