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Status |
Public on Feb 26, 2021 |
Title |
The NK cell stress response status modulates anti-tumor immunity [scRNA-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The tumor microenvironment (TME) comprises numerous forms of cellular stress, which can activate Heat Shock Factor 1 (HSF1), the master transcription factor of the proteotoxic stress response. We profiled HSF1 activity across tumor-infiltrating immune populations, revealing the highest activity in CD8+ T cells and the lowest in natural killer (NK) cells. To elucidate the mechanisms through which HSF1 regulates immune surveillance, we generated an in vivo model of augmented HSF1 activity. Tumor challenge revealed that accumulation of HSF1 dampens NK-mediated tumor immunity and impairs both cytotoxicity and production of interferon gamma (IFN-γ) in NK cells. Single-cell transcriptional profiling identified a loss of anti-tumor signaling pathways, including interferon signaling, within the HSF1-enhanced TME. In NK cells, integration of chromatin accessibility with transcriptomics revealed that HSF1 deregulates accessibility and expression of genes encoding for NK receptors, leading to an inhibitory bias.
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Overall design |
Single-cell RNA-sequencing was performed in tumors engrafted in wild-type (WT) controls and mice bearing serine to alanine mutations in amino acids 303 and 307 (S303/7A). Tumors from 4 mice were pooled for Transcriptomic and epigenetic profiling of NK cells was performed by mRNA sequencing and assay for transposase-accessible chromatin (ATAC) sequencing in splenic NK cells isolated from wild-type and HSF1-enhanced mice under steady state conditions. For RNA-seq, 3 biological replicates of NK cells from WT and S303/7A were used. For ATAC-seq, 4 biological replicates of NK cells from WT and S303/7A mice were used.
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Contributor(s) |
Hockemeyer K, Aifantis I |
Citation missing |
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Submission date |
Feb 25, 2021 |
Last update date |
Mar 01, 2021 |
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) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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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 |
PRJNA704942 |
SRA |
SRP308230 |