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Review
. 2021 May 5:11:666624.
doi: 10.3389/fonc.2021.666624. eCollection 2021.

Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy?

Giuseppe Palmieri  1 , Carla Maria Rozzo  1 , Maria Colombino  2 , Milena Casula  2 , Maria Cristina Sini  2 , Antonella Manca  1 , Marina Pisano  1 , Valentina Doneddu  3 , Panagiotis Paliogiannis  3 , Antonio Cossu  3
Affiliations
Review

Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy?

Giuseppe Palmieri et al. Front Oncol. .

Abstract

The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability-aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)-may exhibit opposite behaviors in terms of immune exclusion or responsiveness. In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.

Keywords: aneuploidy; immunotherapy response; melanoma; microsatellite instability; tumor mutation burden.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Factors determining the total level of mutations in cancer cells. HPV, human papilloma virus; UV, ultraviolet radiation.
Figure 2
Figure 2
Molecular alterations from genetic instability and immune reactivity. CIN, chromosomal instability; MSI, microsatellite instability; SCNA, somatic copy number alteration; TMB, tumor mutation burden.
Figure 3
Figure 3
Distribution of molecular alterations linked to genetic instability in melanoma samples. Numbers indicate the percentages of cases reported in literature (see text for references).
See this image and copyright information in PMC

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