|
KMID : 0370220210650040313
|
|
Yakhak Hoeji
2021 Volume.65 No. 4 p.313 ~ p.320
|
|
|
Characterization of Immune Checkpoint Inhibition Efficacy through Inhibition of Exosome Secretion by Calcium Channel Blockers in Melanoma
|
|
Md Rakibul Alam
Kim Jong-In
Lee Chan-Hyeong
Park Seong-Sik
Baek Moon-Chang
|
|
|
Abstract
|
|
|
Melanoma is a belligerent cutaneous malignancy. Multiple therapeutic options, including immunotherapy andtargeted therapy, have shown remarkable promise in treating metastatic melanoma. Exosomes containing programmed celldeath 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 andfacilitates the growth and proliferation of cancer cells. In this study, we identified nicardipine, an FDA-approved L-typecalcium channel inhibitor, which downregulates the expression of proteins involved in exosome biogenesis and secretionas well as exosomal PD-L1 secretion, from metastatic melanoma cells. Furthermore, nicardipine suppresses PD-L1expression 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 thetreatment of metastatic melanoma.
|
|
|
KEYWORD
|
|
|
Melanoma, Exosomes, PD-L1, Immunosuppression, Calcium channel blocker
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|