Natural Killer Cells Suppress T Cell-Associated Tumor Immune Evasion.
Cell Rep
; 28(11): 2784-2794.e5, 2019 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-31509742
ABSTRACT
Despite the clinical success of cancer immunotherapies, the majority of patients fail to respond or develop resistance through disruption of pathways that promote neo-antigen presentation on MHC I molecules. Here, we conducted a series of unbiased, genome-wide CRISPR/Cas9 screens to identify genes that limit natural killer (NK) cell anti-tumor activity. We identified that genes associated with antigen presentation and/or interferon-γ (IFN-γ) signaling protect tumor cells from NK cell killing. Indeed, Jak1-deficient melanoma cells were sensitized to NK cell killing through attenuated NK cell-derived IFN-γ-driven transcriptional events that regulate MHC I expression. Importantly, tumor cells that became resistant to T cell killing through enrichment of MHC I-deficient clones were highly sensitive to NK cell killing. Taken together, we reveal the genes targeted by tumor cells to drive checkpoint blockade resistance but simultaneously increase their vulnerability to NK cells, unveiling NK cell-based immunotherapies as a strategy to antagonize tumor immune escape.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Linfocitos T
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Antígenos de Histocompatibilidad Clase I
/
Interferón gamma
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Escape del Tumor
/
Melanoma
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Australia