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Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [CRISPR screen]

ABSTRACT: The pleiotropic cytokine interferon-gamma (IFNγ) is known to be associated with cytostatic, anti-proliferation, and pro-apoptosis functions in cancer cells. However, cancer cells can become resistant to IFNγ, and the underlying mechanism is not fully understood. To investigate the potential IFNγ resistant mechanisms, we performed IFNγ sensitivity screens in more than 40 cancer cell lines and characterized the sensitive and resistant cell lines. By applying CRISPR screening and transcriptomic profiling in both IFNγ sensitive and resistant cells, we discovered that activation of double-strand break (DSB) repair genes could result in IFNγ resistance in cancer cells. In addition, suppression of single-strand break (SSB) repair genes increased the essentiality of DSB repair genes after IFNγ treatment. The relationship between the activation of DSB repair genes and IFNγ resistance was further confirmed in clinical tumor profiles from The Cancer Genome Atlas (TCGA) and immune checkpoint blockade (ICB) cohorts. Our study provides a comprehensive resource to elucidate IFNγ resistance in cancer and has the potential to inform combinational therapeutic strategies to overcome immunotherapy resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180942 | GEO | 2023/02/28

REPOSITORIES: GEO

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Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [RNA-seq]

Project description:The pleiotropic cytokine interferon-gamma (IFNγ) is known to be associated with cytostatic, anti-proliferation, and pro-apoptosis functions in cancer cells. However, cancer cells can become resistant to IFNγ, and the underlying mechanism is not fully understood. To investigate the potential IFNγ resistant mechanisms, we performed IFNγ sensitivity screens in more than 40 cancer cell lines and characterized the sensitive and resistant cell lines. By applying CRISPR screening and transcriptomic profiling in both IFNγ sensitive and resistant cells, we discovered that activation of double-strand break (DSB) repair genes could result in IFNγ resistance in cancer cells. In addition, suppression of single-strand break (SSB) repair genes increased the essentiality of DSB repair genes after IFNγ treatment. The relationship between the activation of DSB repair genes and IFNγ resistance was further confirmed in clinical tumor profiles from The Cancer Genome Atlas (TCGA) and immune checkpoint blockade (ICB) cohorts. Our study provides a comprehensive resource to elucidate IFNγ resistance in cancer and has the potential to inform combinational therapeutic strategies to overcome immunotherapy resistance.

2023-02-28 | GSE180941 | GEO

Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity

Project description:Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity

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Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [RNA-seq]

Project description:Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [RNA-seq]

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Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [CRISPR screen]

Project description:Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity [CRISPR screen]

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Ma2005-digital response of p53 to DNA damage-ATM Activation Module

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Quantitative Genomic Analysis of RecA Protein Binding During DNA Double-Strand Break Repair Reveals RecBCD Action in vivo

Project description:Here we have developed a method that combines chromatin immunoprecipitation with next-generation sequencing (ChIP-Seq) and mathematical modeling to quantify RecA protein binding during the active repair of a single DSB in the chromosome of Escherichia coli. Examination of RecA binding during double-strand break repair in Escherichia coli

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Project description:Comparative proteomic analysis identified a total of 452 differentially abundant proteins (DAPs) in the fluorescence-activated cell sorting (FACS) isolated spermatocytes from 12-month-old yak and cattleyak. 291 proteins were only identified in yak spermatocytes. Gene Ontology analysis revealed that the downregulated DAPs were mostly enriched in the cellular response to DNA damage stimulus and double-strand break (DSB) repair via break-induced replication, while the proteins specific for yak were related to cell division and cycle, spermatogenesis, and negative regulation of the extrinsic apoptotic signaling pathway.

2023-03-21 | PXD043039 |

Transcriptional effects of I-PpoI induced DNA double strand breaks in mouse lymphocytes

Project description:DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Using a mouse model for both tissue-specific and temporally controlled DSB formation, we investigated the transcriptional response to break repair. Transcriptional profiling of lymphocytes in spleen and thymus by RNA-Seq, with and without I-PpoI knock-in.

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