Limonta Patrizia, Chiaramonte Raffaella, Casati Lavinia
Department of Pharmacological and Biomolecular Sciences "R. Paoletti", Università degli Studi di Milano, 20133 Milan, Italy.
Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy.
Cancers (Basel). 2024 Aug 16;16(16):2861. doi: 10.3390/cancers16162861.
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.
皮肤黑色素瘤在全球范围内仍然是一个重大的健康负担，占皮肤癌死亡人数的大部分。治疗策略的关键进展显著改善了患者的治疗效果；然而，大多数患者仍会出现耐药性和肿瘤复发。癌症干细胞（CSCs）是包括黑色素瘤在内的不同肿瘤中的一小部分细胞亚群，具有自我更新和分化为大量肿瘤细胞的独特能力。黑色素瘤癌症干细胞的特征在于特定生物标志物的表达和细胞内信号通路；此外，它们在肿瘤的发生、发展和耐药性中起关键作用。近年来，人们付出了巨大努力来剖析黑色素瘤癌症干细胞促肿瘤活性的分子机制，为新型的以癌症干细胞为靶点的治疗提供依据。在此，我们重点介绍黑色素瘤癌症干细胞与肿瘤微环境（TME）中的旁观者细胞（包括免疫细胞、内皮细胞和癌症相关成纤维细胞（CAFs））之间复杂的相互作用，及其在黑色素瘤进展中的作用。具体而言，我们讨论了黑色素瘤癌症干细胞逃避宿主免疫监视、募集免疫抑制细胞以及将免疫细胞诱导为免疫抑制和促肿瘤表型的特殊能力。我们还探讨了目前正在研究的以癌症干细胞为靶点的策略，这些策略可能为黑色素瘤治疗的新的有前景的治疗方法铺平道路。
