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https://doi.org/10.1186/s13046-021-01916-8
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Título: | MITF induces escape from innate immunity in melanoma |
Fecha de publicación: | 2021 |
Editorial: | BMC |
Cita bibliográfica: | Journal of Experimental & Clinical Cancer Research (2021) 40:117 |
ISSN: | Electronic: 1756-9966 |
Materias relacionadas: | CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica |
Palabras clave: | MITF Melanoma ADAM10 NK-cells Anti-tumor immunity |
Resumen: | Background: 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. |
Autor/es principal/es: | Sánchez-Del-Campo, Luis Martí-Díaz, Román Montenegro, María F. González-Guerrero, Rebeca Hernández-Caselles, Trinidad Martínez-Barba, Enrique Piñero-Madrona, Antonio Cabezas-Herrera, Juan Goding, Colin R. Rodríguez-López, José Neptuno |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
URI: | http://hdl.handle.net/10201/138918 |
DOI: | https://doi.org/10.1186/s13046-021-01916-8 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 18 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | © 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. |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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