Melanoma Single-Cell Biology in Experimental and Clinical Settings.

Publication date: Feb 01, 2021

Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8 T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.

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Concepts Keywords
Cellular Tumour heterogeneity
Fibroblasts Microphthalmia-associated transcription factor
Kinase BRAF
Med Melanoma
Melanoma Oncology
Therapy Cancer
Tumor Clinical medicine
CD8 melanoma
Repression melanoma
Deeper insights melanoma
Malignant melanoma
Immune fibroblasts tumor
Subtypes melanoma tumors
Checkpoint inhibitor
Tumor microenvironment
Cancer immunotherapy
Vemurafenib

Semantics

Type Source Name
disease MESH repression
drug DRUGBANK L-Tyrosine
disease MESH microphthalmia
drug DRUGBANK L-Threonine
drug DRUGBANK Serine
disease MESH tumors
pathway KEGG Melanoma
disease MESH Melanoma

Original Article

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