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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 R.
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 B e Inmunología
dc.date.accessioned2024-02-08T08:15:58Z
dc.date.available2024-02-08T08:15:58Z
dc.date.issued2021
dc.description© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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.es
dc.formatapplication/pdfes
dc.format.extent18es
dc.identifier.citationJournal of Experimental & Clinical Cancer Research (2021) 40:117
dc.identifier.doihttps://doi.org/10.1186/s13046-021-01916-8
dc.identifier.issnElectronic: 1756-9966
dc.identifier.urihttp://hdl.handle.net/10201/138918
dc.languageenges
dc.publisherBMCes
dc.relationMinisterio de Economia y Competitividad (MINECO; Co-financing with Fondos FEDER) (SAF2016–77241- R), y Fundación Séneca, Región de Murcia (FS-RM) (20809/PI/18).es
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.subjectMITFen
dc.subjectMelanomaen
dc.subjectADAM10en
dc.subjectNK-cellsen
dc.subjectAnti-tumor immunityen
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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