Inhibition of CD24 Expression Enhances the Anti-Melanoma Effect of Endostatin by Ameliorating Anti-Tumor Immune Responses in Melanoma-Bearing Mice.

INTRODUCTION

Melanoma is a highly aggressive skin cancer that arises from transformed 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 signal, 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 verification. A melanoma-bearing mouse model was used to observe changes in tumor size during treatment. Protein expression, apoptosis, immune cell infiltration, and macrophage subset proportions were measured using Western blot, immunofluorescence, TUNEL, and flow cytometry 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 microenvironment, enhancing M1 macrophage and T lymphocyte infiltration while suppressing angiogenesis via dual inhibition of CD24 and VEGF.

CONCLUSION

Combining CD24 inhibition with antiangiogenic therapy could offer a novel therapeutic strategy for melanoma.