Single-cell RNA sequencing in melanoma: what have we learned so far?

Abstract

Over the past decade, there have been remarkable improvements in the treatment and survival rates of melanoma patients. Treatment resistance remains a persistent challenge, however, and is partly attributable to intratumoural heterogeneity. Melanoma cells can transition through a series of phenotypic and transcriptional cell states that vary in invasiveness and treatment responsiveness. The diverse stromal and immune contexture of the tumour microenvironment also contributes to intratumoural heterogeneity and disparities in treatment response in melanoma patients. Recent advances in single-cell sequencing technologies have enabled a more detailed understanding of melanoma heterogeneity and the underlying transcriptional programs that regulate melanoma cell diversity and behaviour. In this review, we examine the concept of intratumoural heterogeneity and the challenges it poses to achieving long-lasting treatment responses. We focus on the significance of next generation single-cell sequencing in advancing our understanding of melanoma diversity and the unique insights gained from single-cell studies.

Keywords: Cellular states; Dedifferentiation; Immunotherapies; MAPK inhibitors.

Fig. 1

Intratumour heterogeneity is driven by the plasticity of melanoma cells to exist in multiple cells states and the diverse stromal and immune contexture within the tumour.

Fig. 2

Melanoma cell plasticity and transition to diverse transcriptional and phenotypic states defined by key features.