An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.
Cancer Cell
; 36(4): 385-401.e8, 2019 10 14.
Article
en En
| MEDLINE
| ID: mdl-31564637
Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
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Protocolos de Quimioterapia Combinada Antineoplásica
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Regulación Neoplásica de la Expresión Génica
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Escape del Tumor
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Complejo Represivo Polycomb 2
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Neoplasias
Límite:
Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article