Por favor, use este identificador para citar o enlazar este ítem: 10.1186/s13046-021-01916-8

Título: MITF induces escape from innate immunity in melanoma
Fecha de publicación: 31-mar-2021
Editorial: Springer Nature
Cita bibliográfica: Journal of Experimental & Clinical Cancer Research. Volumen: 40 ,nº: 117, 2021
ISSN: 1756-9966
Materias relacionadas: CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
Palabras clave: Melanoma
Inmune system
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. Background
Autor/es principal/es: Sánchez del Campo Ferrer, Luis
Martí Díaz, Román
Montenegro Arce, María Fernanda
González Guerrero, Rebeca
Hernández Caselles, Trinidad
Martínez Barba, Enrique
Piñero Madrona, Antonio
Cabezas Herrera, Juan
Goding, Colin
Rodríguez López, José Neptuno
Facultad/Departamentos/Servicios: Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular A
Versión del editor: https://doi.org/10.1186/s13046-021-01916-8
URI: http://hdl.handle.net/10201/138352
DOI: 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: ©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
Aparece en las colecciones:Artículos: Bioquímica y Biología Molecular "A"

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