흑색종에서 칼슘 채널 차단제에 의한 엑소좀 분비 억제를 통한 면역 관문 억제 효능 규명

Characterization of Immune Checkpoint Inhibition Efficacy through Inhibition of Exosome Secretion by Calcium Channel Blockers in Melanoma

Melanoma is a belligerent cutaneous malignancy. Multiple therapeutic options, including immunotherapy and targeted therapy, have shown remarkable promise in treating metastatic melanoma. Exosomes containing programmed cell death ligand 1 (PD-L1) secreted from melanoma bind to programmed cell death 1 (PD-1) on the surface of CD8+ T cells. As a result, melanoma not only evades the immune surveillance of CD8+ T cells but also inhibits their activation and facilitates the growth and proliferation of cancer cells. In this study, we identified nicardipine, an FDA-approved L-type calcium channel inhibitor, which downregulates the expression of proteins involved in exosome biogenesis and secretion as well as exosomal PD-L1 secretion, from metastatic melanoma cells. Furthermore, nicardipine suppresses PD-L1 expression after interferon-γ-mediated stimulation and enhances CD8+ cell function, similar to the function of PD-L1- blocking antibodies in cancer therapies. This could lead to the development of next-generation anticancer drugs for the treatment of metastatic melanoma.