Introduction: Melanoma is a highly aggressive skin cancer that arises from trans-formed epidermal melanocytes and is one of the malignancies with the fastest proliferation rates globally. Angiogenesis has been identified as a critical target for melanoma therapy, and endostatin has been verified to impede endogenous angiogenesis. However, some patients' therapeutic responses remain unsatisfactory. CD24, which functions as an anti-phagocytic sig-nal, represents a potential target for tumor immunotherapy. Thus, in this study, we investigated the anti-melanoma effects of combined CD24 inhibition and endostatin treatment. Materials and Methods: The co-expressed plasmid was constructed for functional verifica-tion. A melanoma-bearing mouse model was used to observe changes in tumor size during treatment. Protein expression, apoptosis, immune cell infiltration, and macrophage subset pro-portions were measured using Western blot, immunofluorescence, TUNEL, and flow cytom-etry assays. Results: The co-expressed plasmid significantly inhibited CD24 and VEGF expression in cells. The combination therapy promoted tumor cell apoptosis and decreased angiogenesis. It also increased infiltration of M1 macrophages, T lymphocytes, and NK cells in tumor tissue and the spleen. The combined plasmid-based therapy considerably suppressed tumor growth and lengthened the survival time of mice. Discussion: The combination therapy remodeled the immunosuppressive tumor microenvi-ronment, enhancing M1 macrophage and T lymphocyte infiltration while suppressing angio-genesis via dual inhibition of CD24 and VEGF. Conclusion: Combining CD24 inhibition with antiangiogenic therapy could offer a novel ther-apeutic strategy for melanoma.
Lei et al. (Mon,) studied this question.