Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care.
皮肤黑色素瘤仍是全球范围内重要的健康负担，其导致的死亡占皮肤癌死亡病例的绝大多数。治疗策略的关键进展显著改善了患者预后，但多数患者仍面临耐药性与肿瘤复发问题。癌症干细胞作为包括黑色素瘤在内的多种肿瘤中的微小细胞亚群，具有自我更新及分化为主体肿瘤细胞的独特能力。黑色素瘤干细胞以特异性生物标志物表达及细胞内信号通路为特征，并在肿瘤发生、进展及耐药过程中发挥关键作用。近年来，学界致力于解析黑色素瘤干细胞促肿瘤活性的分子机制，为开发新型靶向治疗奠定基础。本文重点阐述黑色素瘤干细胞与肿瘤微环境中旁观细胞（包括免疫细胞、内皮细胞及癌症相关成纤维细胞）之间复杂的相互作用网络及其在黑色素瘤进展中的作用机制。特别探讨了黑色素瘤干细胞逃逸宿主免疫监视、招募免疫抑制细胞、诱导免疫细胞向免疫抑制及促肿瘤表型转化的特殊能力。同时评述当前正在研究的癌症干细胞靶向策略，这些研究可能为黑色素瘤治疗开辟新的前景。
肿瘤(癌症)患者之家