LGALS9 blockade augments vaccine-induced immune responses against prostate cancer

BACKGROUND: Prostate-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. METHODS: Recombinant 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. RESULTS: T-cell responses that conferred protection against tumor rechallenge. CONCLUSIONS: T-cell immunity and synergistically augments the therapeutic efficacy of tumor vaccines, representing a promising immunotherapeutic strategy for prostate cancer.