Amlodipine as an immunomodulator to enhance dendritic cell activation in cancer therapy with tumor-associated antigens.

This study explores the immunomodulatory effects of amlodipine, a widely used antihypertensive, on dendritic cell (DC) maturation and anti-tumor immunity. Using flow cytometry, ELISA, and single-cell RNA sequencing, we found that amlodipine significantly promotes DC maturation, evidenced by increased CD80 and CD86 expression and upregulation of genes like CCL4 and Saa3 related to T cell activation. Furthermore, when amlodipine was administered in conjunction with indocyanine green or doxorubicin therapy in murine models of 4T1 breast cancer and CT26 colon cancer, we observed a notable activation of CD8(+) T cells. This combination therapy also resulted in elevated serum levels of cytokines such as tumor necrosis factor α, interferon-γ, and interleukin-12 and the upregulation of CD8(+) effector memory T cells indicative of a robust systemic immune activation, which ultimately contributed to the inhibition of tumor growth and a decrease in lung metastasis. Our research elucidates the immunomodulatory role of amlodipine in enhancing DC maturation and anti-tumor immune responses, suggesting a promising avenue for future cancer immunotherapy strategies and warranting further investigation in clinical trials.