Graduate Program in Cellular and Molecular Pharmacology, School of Graduate Studies Rutgers University, Piscataway, NJ 08854, USA.
Susan Lehman Cullman Laboratory for Cancer Research, Rutgers University, Piscataway, NJ 08854, USA.
Int J Mol Sci. 2020 Nov 26;21(23):8984. doi: 10.3390/ijms21238984.
Melanoma is the most aggressive and dangerous form of skin cancer that develops from transformed melanocytes. It is crucial to identify melanoma at its early stages, in situ, as it is "curable" at this stage. However, after metastasis, it is difficult to treat and the five-year survival is only 25%. In recent years, a better understanding of the etiology of melanoma and its progression has made it possible for the development of targeted therapeutics, such as vemurafenib and immunotherapies, to treat advanced melanomas. In this review, we focus on the molecular mechanisms that mediate melanoma development and progression, with a special focus on the immune evasion strategies utilized by melanomas, to evade host immune surveillances. The proposed mechanism of action and the roles of immunotherapeutic agents, ipilimumab, nivolumab, pembrolizumab, and atezolizumab, adoptive T- cell therapy plus T-VEC in the treatment of advanced melanoma are discussed. In this review, we implore that a better understanding of the steps that mediate melanoma onset and progression, immune evasion strategies exploited by these tumor cells, and the identification of biomarkers to predict treatment response are critical in the design of improved strategies to improve clinical outcomes for patients with this deadly disease.
黑色素瘤是最具侵袭性和危险性的皮肤癌，源于转化的黑素细胞。在原位及早发现黑色素瘤至关重要，因为此时它是“可治愈的”。然而，一旦发生转移，治疗就变得困难，五年生存率仅为 25%。近年来，对黑色素瘤病因及其进展的更好理解使得靶向治疗（如vemurafenib 和免疫疗法）得以开发，用于治疗晚期黑色素瘤。在这篇综述中，我们重点关注介导黑色素瘤发生和进展的分子机制，特别关注黑色素瘤用于逃避宿主免疫监视的免疫逃逸策略。讨论了提议的作用机制和免疫治疗药物 ipilimumab、nivolumab、pembrolizumab 和 atezolizumab、过继性 T 细胞疗法加 T-VEC 在治疗晚期黑色素瘤中的作用。在这篇综述中，我们恳请更好地理解介导黑色素瘤发病和进展的步骤、这些肿瘤细胞利用的免疫逃逸策略以及鉴定预测治疗反应的生物标志物，这对于设计改善策略以提高患有这种致命疾病的患者的临床结果至关重要。
