Overcoming Immune Evasion in Melanoma

Int J Mol Sci. 2020 Nov 26;21(23):8984. doi: 10.3390/ijms21238984.

Abstract

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.

Keywords: T-VEC; adoptive T-cell therapy; anti-CTLA-4; anti-PD-1; anti-PD-L1; immune checkpoint blockade therapy; immunotherapy; melanoma; melanoma immune evasion.

Publication types

  • Review

MeSH terms

  • Humans
  • Immune Evasion*
  • Immunotherapy
  • Melanoma / diagnosis
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy
  • Risk Factors
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Tumor Microenvironment