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The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to govern anti-tumor immunity

ABSTRACT: Pcif1 KO mice can significantly inhibit tumor growth. We attempted to explore the changes in tumor immune microenvironment of tumor-bearing mice after Pcif1 KO by single-cell sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE254353 | GEO | 2024/11/14

REPOSITORIES: GEO

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The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to govern anti-tumor immunity

Project description:T cell-based cancer immunotherapies have revolutionized cancer treatment, yet durable responses remain elusive. Here, we report that PCIF1, an RNA N6, 2’-O-dimethyladenosine (m6Am) methyltransferase, negatively regulates CD8+ T cell anti-tumor responses. Whole-body or T cell-specific Pcif1 knockout (KO) significantly reduces tumor growth in mice. Single-cell RNA sequencing reveals heightened tumor-infiltrating cytotoxic CD8+ T cells in Pcif1-deficient mice. Mechanistically, proteomic and m6Am-sequencing analyses pinpoint that Pcif1 KO elevates crucial m6Am-modified targets, specifically ferroptosis suppressor genes (Fth1, Slc3a2), and T cell activation gene Cd69, imparting resistance to ferroptosis and enhancing CD8+ T cell activation. Of note, Pcif1-deficient mice with tumors exhibit enhanced responses to anti-PD-1 immunotherapy, and Pcif1 KO CAR T cells demonstrate improved tumor control. Clinically, cancer patients with low PCIF1 expression in T cells exhibit enhanced responses to immunotherapies. These findings suggest that PCIF1 suppresses CD8+ T cell activation and targeting PCIF1 as a promising strategy to boost anti-tumor immunity.

2024-11-14 | GSE254597 | GEO

The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to govern anti-tumor immunity

Project description:The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to govern anti-tumor immunity

| PRJNA1071102 | ENA

Pro-Seq of MEL624 control and PCIF1 KO cells

Project description:We analyzed human melanoma cells by PRO-Seq in order to determine the effect of PCIF1 KO in Pol II dynamics

2019-06-01 | GSE122802 | GEO

m6A MeRIP-Seq of MEL624 control and PCIF1 KO cells

Project description:We analyzed m6A distribution by m6A MeRIP in otder to determine the effect of PCIF1 KO over m6A distribution in human melanoma cells

2019-06-01 | GSE122801 | GEO

HIV reprograms host m6Am RNA methylome by viral Vpr protein-mediated degradation of PCIF1

Project description:To identify m6Am genes that are responsible for HIV inhibition, m6Am-exo-seq was performed in control, PCIF1 KO T cells, and cells infected with HIV.

2021-08-09 | GSE171800 | GEO

m6Am RNA methylation enzyme PCIF1 restricts HIV infection and is degraded by viral Vpr protein

Project description:To identify m6Am genes that are responsible for HIV inhibition, MeRIP-seq was performed in control and PCIF1 KO T cells infected with HIV.

2021-08-09 | GSE154035 | GEO

m6A-seq data analysis of control and PCIF1 knockdown transcriptome

Project description:Purpose: To identify the in vivo RNA targets of PCIF1, we performed meRIP experiments for PCIF1 KD and control cells using an anti-m6A antibody. We envisioned that the cap-specific PCIF1 should selectively alter the m6Am modification at the 5-terminal region of transcripts. Indeed, we observed a reduction of modification peaks at the 5’-end but not the 3’-UTR regions of mRNA upon PCIF1 KD.

2018-12-20 | GSE120229 | GEO

Effect of PCIF1 knockdown on gene exppression in HeLa S3 cells

Project description:We previously identified PCIF1 (Phosphorylated CTD Interacting Factor 1) as a novel phosphorylated C-terminal domain (CTD) of RNA polymerase II. We also recently identified PCIF1 as a new cap-specific adenine N6 methyltransferase (CAPAM) responsible for creating N6, 2’-O-dimethyladenosine (m6Am) at the 5’-end of mRNAs. However, it remains unclear how PCIF1 regulates gene expression. To identify genes whose expression levels are affected by PCIF1 knockdown in human cultured cells, we performed gene expression profiling by microarray analysis.

2023-09-30 | GSE156768 | GEO

Pro-Seq of MEL624 control and PCIF1 KO cells

Project description:Pro-Seq of MEL624 control and PCIF1 KO cells

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Nuclear localization of fly Pcif1 is required for gene regulation and fertility

Project description:Here we show that Pcif1 mutant flies display a reduced fertility which is particularly marked in females. Deep sequencing analysis of Pcif1 mutant ovaries revealed transcriptome changes with a notable increase in expression of genes belonging to the mitochondrial ATP synthetase complex.

2023-03-09 | GSE218059 | GEO

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