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MITF induces escape from innate immunity in melanoma

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dc.contributor.authorMartí Díaz, Román
dc.contributor.authorGonzález Guerrero, Rebeca
dc.contributor.authorMartínez Barba, Enrique
dc.contributor.authorPiñero Madrona, Antonio
dc.contributor.authorCabezas Herrera, Juan
dc.contributor.authorGoding, Colin
dc.contributor.authorMontenegro Arce, María Fernanda
dc.contributor.authorHernández Caselles, Trinidad
dc.contributor.authorRodríguez López, José Neptuno
dc.contributor.authorSánchez del Campo Ferrer, Luis
dc.contributor.departmentBioquímica y Biología Molecular Aes
dc.date.accessioned2024-02-01T11:35:08Z
dc.date.available2024-02-01T11:35:08Z
dc.date.issued2021-03-31
dc.description©2021. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Journal of Experimental & Clinical Cancer Research. To access the final edited and published work see https://doi.org/10.1186/s13046-021-01916-8
dc.description.abstractBackground The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies. Backgroundes
dc.formatapplication/pdfes
dc.format.extent18es
dc.identifier.citationJournal of Experimental & Clinical Cancer Research. Volumen: 40 ,nº: 117, 2021
dc.identifier.doi10.1186/s13046-021-01916-8
dc.identifier.issn1756-9966
dc.identifier.urihttp://hdl.handle.net/10201/138352
dc.languageenges
dc.publisherSpringer Naturees
dc.relationÁmbito del proyecto: Nacional y regional. - Agencia financiadora: Ministerio de Economía y Competitividad (MINECO; Co-financing with Fondos FEDER) y Fundación Séneca, the Región de Murcia (FS-RM)- Código o número del acuerdo de subvención: SAF2016–77241-R, 20809/PI/18, RYC-2016-20036 y 21407/FPI/20es
dc.relation.isreplacedby10.1186/s13046-021-01916-8es
dc.relation.publisherversionhttps://doi.org/10.1186/s13046-021-01916-8es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMelanomaes
dc.subjectInmune systemes
dc.subjectMITFes
dc.subjectADAM10es
dc.subjectAnti-tumor immunity
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísicaes
dc.titleMITF induces escape from innate immunity in melanomaes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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