Melanoma Single-Cell Biology in Experimental and Clinical Settings
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 identi...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-02-01
|
Series: | Journal of Clinical Medicine |
Subjects: | |
Online Access: | https://www.mdpi.com/2077-0383/10/3/506 |
id |
doaj-045335eb674049bf805c68faee568bc3 |
---|---|
record_format |
Article |
spelling |
doaj-045335eb674049bf805c68faee568bc32021-02-02T00:01:05ZengMDPI AGJournal of Clinical Medicine2077-03832021-02-011050650610.3390/jcm10030506Melanoma Single-Cell Biology in Experimental and Clinical SettingsHans Binder0Maria Schmidt1Henry Loeffler-Wirth2Lena Suenke Mortensen3Manfred Kunz4Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, GermanyInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, GermanyInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, GermanyInterdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, GermanyDepartment of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Philipp-Rosenthal-Str. 23-25, 04103 Leipzig, GermanyCellular 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<sup>+</sup> 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.https://www.mdpi.com/2077-0383/10/3/506melanomasingle-cell transcriptome sequencingtreatment responsepseudotime analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hans Binder Maria Schmidt Henry Loeffler-Wirth Lena Suenke Mortensen Manfred Kunz |
spellingShingle |
Hans Binder Maria Schmidt Henry Loeffler-Wirth Lena Suenke Mortensen Manfred Kunz Melanoma Single-Cell Biology in Experimental and Clinical Settings Journal of Clinical Medicine melanoma single-cell transcriptome sequencing treatment response pseudotime analysis |
author_facet |
Hans Binder Maria Schmidt Henry Loeffler-Wirth Lena Suenke Mortensen Manfred Kunz |
author_sort |
Hans Binder |
title |
Melanoma Single-Cell Biology in Experimental and Clinical Settings |
title_short |
Melanoma Single-Cell Biology in Experimental and Clinical Settings |
title_full |
Melanoma Single-Cell Biology in Experimental and Clinical Settings |
title_fullStr |
Melanoma Single-Cell Biology in Experimental and Clinical Settings |
title_full_unstemmed |
Melanoma Single-Cell Biology in Experimental and Clinical Settings |
title_sort |
melanoma single-cell biology in experimental and clinical settings |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2021-02-01 |
description |
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<sup>+</sup> 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. |
topic |
melanoma single-cell transcriptome sequencing treatment response pseudotime analysis |
url |
https://www.mdpi.com/2077-0383/10/3/506 |
work_keys_str_mv |
AT hansbinder melanomasinglecellbiologyinexperimentalandclinicalsettings AT mariaschmidt melanomasinglecellbiologyinexperimentalandclinicalsettings AT henryloefflerwirth melanomasinglecellbiologyinexperimentalandclinicalsettings AT lenasuenkemortensen melanomasinglecellbiologyinexperimentalandclinicalsettings AT manfredkunz melanomasinglecellbiologyinexperimentalandclinicalsettings |
_version_ |
1724314770844155904 |