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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [ATAC-Seq]

ABSTRACT: Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [ATAC-Seq]

PROVIDER: PRJNA638676 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11991576_1.fastq.gz	Fastqsanger.gz
	SRR11991576_2.fastq.gz	Fastqsanger.gz
	SRR11991577_1.fastq.gz	Fastqsanger.gz
	SRR11991577_2.fastq.gz	Fastqsanger.gz
	SRR11991578_1.fastq.gz	Fastqsanger.gz

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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity

Project description:Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity

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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [scRNA-Seq]

Project description:We report here that persistent activation of signal transducer and activator of transcription 5 (STAT5) in tumor-specific CD4+ T cells drives the development of polyfunctional T cells with superior antitumor activities. We showed that ectopic expression of a constitutively active form of murine STAT5A (CASTAT5) in tumor-specific CD4+ T cells established a distinct epigenetic and transcriptional landscape, endowing CD4+ T cells polyfunctionality, exhaustion-resistance and tumor-infiltrating capability. Single cell RNA sequencing analysis (scRNAseq) identified a subset of cells with the molecular signature indicative of their role as progenitor polyfunctional T cells. Importantly, T cells engineered to co-express CD19-targeting chimeric antigen receptors (CD19CAR) and CASTAT5 gave rise to polyfunctional CD4+ CAR T cells capable of providing optimal help to CD8+ T cells to achieve durable and curative outcomes in mice with advanced B-cell lymphoma. Evidence of CASTAT5 functional activities in primary human CD4+ T cells underscores its potential clinical relevance.

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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [RNA-Seq]

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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [ATAC-Seq]

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Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [RNA-Seq]

Project description:Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [RNA-Seq]

| PRJNA638675 | ENA

Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [scRNA-Seq]

Project description:Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity [scRNA-Seq]

| PRJNA638677 | ENA

Persistent STAT5 activation reprograms the epigenetic landscape in CD4<sup>+</sup> T cells to drive polyfunctionality and antitumor immunity.

Project description:The presence of polyfunctional CD4+ T cells is often associated with favorable antitumor immunity. We report here that persistent activation of signal transducer and activator of transcription 5 (STAT5) in tumor-specific CD4+ T cells drives the development of polyfunctional T cells. We showed that ectopic expression of a constitutively active form of murine STAT5A (CASTAT5) enabled tumor-specific CD4+ T cells to undergo robust expansion, infiltrate tumors vigorously, and elicit antitumor CD8+ T cell responses in a CD4+ T cell adoptive transfer model system. Integrated epigenomic and transcriptomic analysis revealed that CASTAT5 induced genome-wide chromatin remodeling in CD4+ T cells and established a distinct epigenetic and transcriptional landscape. Single-cell RNA sequencing analysis further identified a subset of CASTAT5-transduced CD4+ T cells with a molecular signature indicative of progenitor polyfunctional T cells. The therapeutic significance of CASTAT5 came from our finding that adoptive transfer of T cells engineered to coexpress CD19-targeting chimeric antigen receptor (CAR) and CASTAT5 gave rise to polyfunctional CD4+ CAR T cells in a mouse B cell lymphoma model. The optimal therapeutic outcome was obtained when both CD4+ and CD8+ CAR T cells were transduced with CASTAT5, indicating that CASTAT5 facilitates productive CD4 help to CD8+ T cells. Furthermore, we provide evidence that CASTAT5 is functional in primary human CD4+ T cells, underscoring its potential clinical relevance. Our results implicate STAT5 as a valid candidate for T cell engineering to generate polyfunctional, exhaustion-resistant, and tumor-tropic antitumor CD4+ T cells to potentiate adoptive T cell therapy for cancer.

| S-EPMC8265158 | biostudies-literature

Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity

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

2020-10-22 | GSE152242 | GEO

Single-cell transcriptomic sequencing identifies the genes related to polyfunctionality of persistent CAR-T cells targeting B7-H3 (CD276) in mice bearing human neuroblastoma xenografts

Project description:To understand the molecular determinants of B12(VHH)-CAR-T polyfunctionality, we simultaneously measured the protein and RNA expression levels of 95 single CD4+ B12(VHH)-CAR-T cells isolated from IMR5 tumor-bearing mouse and re-stimulated with IMR5 tumor cells in vitro. We identified two CAR-T clusters, low polyfunctionality and high polyfunctionality subsets, in a 2D t-SNE plot. Moreover, our single-cell mRNA expression profiling revealed 32 genes that displayed statistically significant, concordant differences between the two cell subsets.

2023-08-17 | GSE221411 | GEO

Murine Osteoclasts: Stat5 flox vs. Stat5 cKO

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