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In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion.

ABSTRACT: In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion.

PROVIDER: PRJNA1211115 | ENA |

REPOSITORIES: ENA

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In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion.

Project description:Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a high unmet need for enhancing immunotherapy given current modest responses. Here, we performed an in vivo CRISPR screen in a HNSCC mouse model to identify immune evasion genes. We identified several epigenetic regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increased CD8+ T cell infiltration and improved ICB responses. Uchl5 deficiency reduced extracellular matrix (ECM) production and epithelial-mesenchymal-transition (EMT) transcriptional signatures, which contribute to stromal desmoplasia, a histologic finding associated with reduced anti-PD1 response in human HNSCCs. We identified a functional role for COL17A1, a collagen highly and specifically expressed in HNSCC, in Uchl5-mediated immune evasion. Our findings suggest an unappreciated role for UCHL5 in promoting EMT in HNSCC and highlight ECM modulation as a strategy to improve immunotherapy responses.

2025-08-14 | GSE287094 | GEO

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vivo]

2025-06-07 | GSE269445 | GEO

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vitro]

2025-06-07 | GSE269444 | GEO

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion

Project description:In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion

| PRJNA1121930 | ENA

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vivo]

Project description:In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vivo]

| PRJNA1121933 | ENA

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vitro]

Project description:In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vitro]

| PRJNA1121934 | ENA

In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-06-07 | GSE269446 | GEO

UCHL5 promotes Tumorigenesis of Bladder Cancer by Activating AKT/mTOR signaling pathway and targeting c-myc, SLC25A19, and ICAM5.

Project description:Purpose: To investigate the tumor-promoting role of UCHL5 in bladder cancer. Method: We established the UCHL5 knockdown cell line in which the target gene was knocked down by shRNA. RNA was extracted from cells using trizol reagent(Invitrogen) Result: Through RNA-sequencing analysis of wild-type and UCHL5 deficient T24 cell lines, the downstream signaling pathways that UCHL5 may be involved in were determined. We found that the AKT/mTOR signaling pathway and c-Myc,SLC25A19, and ICAM5 were significantly inactivated when UCHL5 was knocked down in bladder cancer. Conclusion: UCHL5 enhances the AKT/mTOR pathway, which consequently upgraded the expression of c-myc,SLC25A19, and ICAM5, ultimately promoting the occurrence and progression of bladder cancer. UCHL5 may suggest potential utility for bladder cancer therapy.

2025-08-02 | GSE211924 | GEO

Stress Keratin 17 mediates immune evasion in head and neck cancer

Project description:Stress Keratin 17 mediates immune evasion in head and neck cancer

| PRJNA754206 | ENA

In vivo CRISPR screens reveal NOTCH regulators suppressing Head and Neck Squamous Cell Carcinoma in mice [Cut&Run]

Project description:In most cancers, only a few genes are mutated at high frequencies, while the vast majority are mutated at low frequencies. The functions of these recurrent but infrequent ‘long-tail’ mutations remain largely elusive. Here, we develop in vivo CRISPR screens to assess the transforming potential of 484 long-tail genes in human Head and Neck Squamous Cell 5 Carcinoma (HNSCC).

2020-02-04 | GSE140496 | GEO

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