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| Status |
Public on Jan 26, 2022 |
| Title |
The NK cell stress response status modulates anti-tumor immunity [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The tumor microenvironment (TME) harbors numerous types of cellular stress that can activate Heat Shock Factor 1 (HSF1), a central regulator of stress response. HSF1 has been shown to directly regulate diverse gene programs beyond the classical heat shock response in a cell-type- and context-specific manner. Here, we uncover significant variability in HSF1 levels and activity between immune populations in patient tumors, with the lowest in natural killer (NK) cells. We demonstrate that accumulation of activated HSF1 in the TME dampens anti-tumor immunity through impairing NK cell cytotoxicity, which could be rescued by NK cells with homeostatic levels of HSF1. HSF1 stabilization results in altered chromatin accessibility and expression of surface receptors and signaling proteins involved in NK cell activation. We further reveal direct occupancy of HSF1 at promoters of genes encoding mediators of NK cell cytotoxicity. Single-cell transcriptional profiling of the TME in the context of elevated HSF1 revealed an inverse relationship between the stress response status and NK cell effector function. Collectively, this work identifies a novel role of HSF1 in regulating the NK cell activation state and subsequent anti-tumor functionality.
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| Overall design |
Chromatin immunoprecipitation (ChIP) for HSF1 was performed in the NK cell line NK-92 MI (10 x 10^6 cells). HSF1 ChIP and input subsequently were sequenced using Novaseq 6000.
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| Contributor(s) |
Hockemeyer K, Battistello E, Aifantis I |
| Citation missing |
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| Submission date |
Jan 25, 2022 |
| Last update date |
May 28, 2024 |
| Contact name |
Kathryn Grace Hockemeyer |
| Organization name |
NYU Langone Health
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| Department |
Pathology
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| Lab |
Aifantis
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| Street address |
550 1st Avenue
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE167552 |
The stress response regulator HSF1 modulates natural killer cell anti-tumour immunity |
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| Relations |
| BioProject |
PRJNA800365 |
