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Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in HCC [scRNA-seq]

ABSTRACT: We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of PD-1 therapy responsive and resistant patients samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208307 | GEO | 2025/11/14

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE208307_MarkerGenes.csv.gz	Csv
	GSE208307_RAW.tar	Raw
	filelist.txt	Txt

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Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in HCC

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

2025-11-14 | GSE208308 | GEO

Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in HCC [CRISPR screen]

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Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in HCC

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Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in HCC [CRISPR screen]

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Targeting USP14 Enhances Immunotherapy Response by Reprogramming Tumor-Associated Macrophages in Colon Cancer

Project description:Combining immunotherapy with other treatments improves survival in colorectal cancer, yet some patients remain unresponsive. Tumor-associated macrophages (TAMs) are a key immune cell population driving this immunotherapy resistance and fostering an immunosuppressive microenvironment. To overcome this, we screened a deubiquitinating enzyme (DUB) library targeting TAMs and identified USP14 as specifically upregulated in TAMs. Inhibiting USP14 reversed their pro-tumor functions, promoted M1 polarization, enhanced tumor cell killing, and activated effector T cells. USP14 inhibition also increased PD-L1 expression on tumor cells, alleviating T-cell suppression. In vivo, combining a USP14 inhibitor with an anti-PD-1 antibody synergistically enhanced immunotherapy efficacy, suppressed tumor progression, and improved survival in a mouse colon cancer model. Thus, USP14 is a promising target to overcome immunotherapy resistance in colorectal cancer.

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