Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance
Melanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This is ref...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1601 |
| _version_ | 1797441183520129024 |
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| author | Sultana Mehbuba Hossain Michael R. Eccles |
| author_facet | Sultana Mehbuba Hossain Michael R. Eccles |
| author_sort | Sultana Mehbuba Hossain |
| collection | DOAJ |
| description | Melanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This is referred to as phenotype switching in melanoma, and it involves switching between quiescent and proliferative cell cycle states, and dramatic shifts in invasiveness, as well as changes in signaling pathways in the melanoma cells, and immune cell composition in the TME. Melanoma cell plasticity is associated with altered gene expression in immune cells and cancer-associated fibroblasts, as well as changes in extracellular matrix, which drive the metastatic cascade and therapeutic resistance. Therefore, resistance to therapy in melanoma is not only dependent on genetic evolution, but it has also been suggested to be driven by gene expression changes and adaptive phenotypic cell plasticity. This review discusses recent findings in melanoma phenotype switching, immunotherapy resistance, and the balancing of the homeostatic TME between the different melanoma cell subpopulations. We also discuss future perspectives of the biology of neural crest-like state(s) in melanoma. |
| first_indexed | 2024-03-09T12:19:19Z |
| format | Article |
| id | doaj.art-e33542351e0a4b77abf29e63b712455b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:19:19Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e33542351e0a4b77abf29e63b712455b2023-11-30T22:42:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242160110.3390/ijms24021601Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug ResistanceSultana Mehbuba Hossain0Michael R. Eccles1Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandMelanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This is referred to as phenotype switching in melanoma, and it involves switching between quiescent and proliferative cell cycle states, and dramatic shifts in invasiveness, as well as changes in signaling pathways in the melanoma cells, and immune cell composition in the TME. Melanoma cell plasticity is associated with altered gene expression in immune cells and cancer-associated fibroblasts, as well as changes in extracellular matrix, which drive the metastatic cascade and therapeutic resistance. Therefore, resistance to therapy in melanoma is not only dependent on genetic evolution, but it has also been suggested to be driven by gene expression changes and adaptive phenotypic cell plasticity. This review discusses recent findings in melanoma phenotype switching, immunotherapy resistance, and the balancing of the homeostatic TME between the different melanoma cell subpopulations. We also discuss future perspectives of the biology of neural crest-like state(s) in melanoma.https://www.mdpi.com/1422-0067/24/2/1601melanomaphenotypic plasticityepithelial–mesenchymal transitionheterogeneityresistanceMITF |
| spellingShingle | Sultana Mehbuba Hossain Michael R. Eccles Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance International Journal of Molecular Sciences melanoma phenotypic plasticity epithelial–mesenchymal transition heterogeneity resistance MITF |
| title | Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance |
| title_full | Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance |
| title_fullStr | Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance |
| title_full_unstemmed | Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance |
| title_short | Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance |
| title_sort | phenotype switching and the melanoma microenvironment impact on immunotherapy and drug resistance |
| topic | melanoma phenotypic plasticity epithelial–mesenchymal transition heterogeneity resistance MITF |
| url | https://www.mdpi.com/1422-0067/24/2/1601 |
| work_keys_str_mv | AT sultanamehbubahossain phenotypeswitchingandthemelanomamicroenvironmentimpactonimmunotherapyanddrugresistance AT michaelreccles phenotypeswitchingandthemelanomamicroenvironmentimpactonimmunotherapyanddrugresistance |