黑色素瘤是一种高度侵袭性的皮肤癌。癌症干细胞（CSC）的存在和肿瘤免疫逃避是黑色素瘤进展的两个主要原因，但目前尚未找到有效的治疗方法。黄芪多糖（APS）是从黄芪中提取的主要活性成分，对包括黑色素瘤在内的多种肿瘤具有抗肿瘤作用。然而，其潜在机制仍不清楚。通过肿瘤球形成和致瘤性测定、RT-qPCR 和蛋白质印迹来测量 APS 对黑色素瘤干细胞 (MSC) 自我更新能力和 CSC 标志物表达的调节。采用流式细胞术评估 APS 对黑色素瘤小鼠免疫系统的激活作用。进一步，基于PD-L1过表达和敲低B16细胞探讨了其机制。APS在体外减弱MSCs的肿瘤球形成以及在体内的致瘤性。它还降低了 CD133、BMI1 和 CD47 的表达。基于PD-L1过表达和敲低B16细胞，证实APS通过下调PD-L1表达来抑制MSCs的诱导。同时，APS由于对PD-L1的抑制作用，增加了肿瘤组织中CD4和CD8 T细胞的浸润。APS通过降低PD-L1的表达来抑制MSC的诱导，克服肿瘤的免疫逃逸。这项研究提供了令人信服的证据，表明 APS 可能成为治疗黑色素瘤的前瞻性治疗剂。© 2024。作者。

Melanoma is a highly aggressive form of skin cancer. The existence of cancer stem cells (CSCs) and tumor immune evasion are two major causes of melanoma progression, but no effective treatment has been found at present. Astragalus polysaccharide (APS) is a principal active component derived from Astragalus membranaceus, showing anti-tumor effects in various tumors including melanoma. However, the underlying mechanism is still unclear.The regulation of APS on self-renewal ability and CSC markers expression in melanoma stem cells (MSCs) was measured by tumor sphere formation and tumorigenicity assays, RT-qPCR, and western blot. Flow cytometry was conducted to evaluate the activation of immune system by APS in melanoma mice. Further, the mechanism was explored based on PD-L1 overexpression and knock-down B16 cells.APS attenuated the tumor sphere formation of MSCs in vitro as well as the tumorigenicity in vivo. It also decreased the expression of CD133, BMI1 and CD47. Based on the PD-L1 overexpression and knock-down B16 cells, it was confirmed that APS inhibited the induction of MSCs by down-regulating PD-L1 expression. Meanwhile, APS increased the infiltration of CD4+ and CD8+T cells in tumor tissues because of its inhibitory effect on PD-L1.APS inhibited MSC induction and overcame tumor immune evasion through reducing PD-L1 expression. This study provided compelling evidence that APS could be a prospective therapeutic agent for treating melanoma.© 2024. The Author(s).