引言：在皮肤癌中，黑色素瘤的死亡率较高。免疫疗法的最新进展，特别是通过免疫检查点调节，已经改善了黑色素瘤的临床治疗。麦芽醇具有多种生物活性，包括抗氧化和抗炎性能，但麦芽醇的抗黑色素瘤性能尚未得到充分的探索。本研究旨在通过调节免疫检查点探索麦芽醇对黑色素瘤的抗肿瘤潜力。 方法：使用qPCR，免疫印迹和免疫荧光分析免疫检查点PD-L1。通过使用CTLL-2细胞进行细胞毒性、细胞存活和IL-2测定来研究黑色素瘤对T细胞的敏感性。 结果：发现麦芽醇能够降低黑色素含量、酪氨酸酶活性和酪氨酸酶及酪氨酸酶相关蛋白1的表达水平。此外，麦芽醇抑制了B16F10的增殖能力，并诱导了细胞周期阻滞。麦芽醇通过提高剪切半胱天冬酶3和PARP的水平增加了细胞凋亡率。麦芽醇与顺铂的联合治疗对抑制生长和促进凋亡具有协同作用。麦芽醇通过减弱STAT1磷酸化来抑制IFN-γ诱导的PD-L1和顺铂上调的PD-L1，并增强对B16F10的顺铂细胞毒性作用。麦芽醇增强了对CTLL-2细胞调控的黑色素瘤破坏的敏感性，导致IL-2产生量的增加。 讨论：这些发现表明，麦芽醇通过下调PD-L1限制了黑色素瘤的生长，并引发T细胞介导的抗癌反应，克服了顺铂介导的PD-L1免疫疗法耐药性。因此，麦芽醇可以被认为是黑色素瘤的有效治疗药物。 版权所有© 2023年 Han, Park, Ko and Moon.

Introduction: Among skin cancers, melanoma has a high mortality rate. Recent advances in immunotherapy, particularly through immune checkpoint modulation, have improved the clinical treatment of melanoma. Maltol has various bioactivities, including anti-oxidant and anti-inflammatory properties, but the anti-melanoma property of maltol remains underexplored. The aim of this work is to explore the anti-melanoma potential of maltol through regulating immune checkpoints. Methods: The immune checkpoint PD-L1 was analyzed using qPCR, immunoblots, and immunofluorescence. Melanoma sensitivity towards T cells was investigated via cytotoxicity, cell viability, and IL-2 assays employing CTLL-2 cells. Results: Maltol was found to reduce melanin contents, tyrosinase activity, and expression levels of tyrosinase and tyrosinase-related protein 1. Additionally, maltol suppressed the proliferative capacity of B16F10 and induced cell cycle arrest. Maltol increased apoptotic rates by elevating cleaved caspase-3 and PARP. The co-treatment with maltol and cisplatin revealed a synergistic effect on inhibiting growth and promoting apoptosis. Maltol suppressed IFN-γ-induced PD-L1 and cisplatin-upregulated PD-L1 by attenuating STAT1 phosphorylation, thereby enhancing cisplatin's cytotoxicity against B16F10. Maltol augmented sensitivity to CTLL-2 cell-regulated melanoma destruction, leading to an increase in IL-2 production. Discussion: These findings demonstrate that maltol restricts melanoma growth through the downregulation of PD-L1 and elicits T cell-mediated anti-cancer responses, overcoming PD-L1-mediated immunotherapy resistance of cisplatin. Therefore, maltol can be considered as an effective therapeutic agent against melanoma.Copyright © 2023 Han, Park, Ko and Moon.