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Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [Microarray Expression]

ABSTRACT: Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [Microarray Expression]

PROVIDER: PRJNA647751 | ENA |

REPOSITORIES: ENA

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Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL

Project description:Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL

| PRJNA648158 | ENA

Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [WGBS]

Project description:Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [WGBS]

| PRJNA719647 | ENA

Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [WGBS]

Project description:Defciency of Regnase-1 enhances CAR-T cell persistence and anti-tumor ability

2021-07-21 | GSE171442 | GEO

Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL.

Project description:Chimeric antigen receptor (CAR)-T-cell therapeutic efficacy is associated with long-term T-cell persistence and acquisition of memory. Memory-subset formation requires T-cell factor 1 (TCF-1), a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B-cell acute lymphoblastic leukemia (ALL; B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR-T-cell expansion and memory-like cell formation. This leads to improved CAR-T-mediated tumor clearance, sustained remissions, and protection against secondary tumor challenge. Phenotypic, transcriptional, and epigenetic profiling identified increased tumor-dependent programming of Regnase-1-deficient CAR-T cells into TCF-1+ precursor exhausted T cells (TPEX) characterized by upregulation of both memory and exhaustion markers. Regnase-1 directly targets Tcf7 messenger RNA (mRNA); its deficiency augments TCF-1 expression leading to the formation of TPEX that support long-term CAR-T-cell persistence and function. Regnase-1 deficiency also reduces exhaustion and enhances the activity of TCF-1- CAR-T cells. We further validate these findings in human CAR-T cells, where Regnase-1 deficiency mediates enhanced tumor clearance in a xenograft B-ALL model. This is associated with increased persistence and expansion of a TCF-1+ CAR-T-cell population. Our findings demonstrate the pivotal roles of TPEX, Regnase-1, and TCF-1 in mediating CAR-T-cell persistence and recall responses, and identify Regnase-1 as a modulator of human CAR-T-cell longevity and potency that may be manipulated for improved therapeutic efficacy.

| S-EPMC8288655 | biostudies-literature

Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL [Microarray Expression]

Project description:transcriptional profiling was performed on WT and KO CAR T cells isolated 7 days after co-transfer into mice with or without tumors. Regnase-1 KO CAR T cells undergoing a tumor-dependent shift from an effector to memory-like phenotype

2021-07-08 | GSE154859 | GEO

Improved persistence and expanded TPEX formation in Regnase-1 KO CAR T cells is TCF-1-dependent

Project description:transcriptional profiling was performed on Regnase-1 KO CAR and Regnase-1 TCF-1 DKO CAR T cells isolated 7days after co-transfer into tumor bearing mice. TCF-1 deficiency in Regnase-1 KO CAR T cells led to reduced long-term persistence and memory-like phenotype.

2021-04-07 | GSE155020 | GEO

Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL

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

2021-04-07 | GSE155021 | GEO

Zheng W, Wei J, Zebley CC, et al. Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL. Blood. 2021;138(2):122-135.

Project description: Not available

| S-EPMC8952182 | biostudies-literature

Single-cell RNA-seq of human breast tumor samples with exhausted and non-exhausted immune environments

Project description:Fresh human breast tumor tissue was dissociated into single cells and viably frozen. Patient samples were annotated as having an ""exhausted"" or ""non-exhausted"" immune environment based on CyTOF characterization of T cell phenotypes (Wagner et al, Cell 2019). 14 samples (7 exhausted, 7 non-exhausted) were selected for scRNA-seq (without prior cell type enrichment) with the goal to compare the two immune environment types and to comprehensively characterize exhaustion-associated features of the tumor microenvironment.

2023-08-25 | E-MTAB-10607 | biostudies-arrayexpress

Crosstalk between the RNA-binding proteins Regnase-1 and -3 shapes mast cell survival and cytokine expression

Project description:Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) impacts immune cell responses, including mast cell functionality. Despite their importance in immune regulation, the functional role of most RBPs remains to be understood. By manipulating the expression of specific RBPs in murine mast cells, coupled with mass spectrometry and transcriptomic analyses, we found that the Regnase family of proteins acts as a potent regulator of mast cell physiology. Specifically, Regnase-1 is required to maintain basic cell proliferation and survival, while both Regnase-1 and -3 cooperatively regulate the expression of inflammatory transcripts upon activation, with Tnf being a primary target in both human and mouse cells. Further, Regnase-3 directly interacts with Regnase-1 in mast cells and is necessary to restrain Regnase-1 expression through the destabilization of its transcript. Overall, our study identifies protein interactors of endogenously expressed Regnase factors, characterizes the regulatory interplay between Regnase family members in mast cells, and establishes their role in the control of mast cell homeostasis and inflammatory responses.

2024-05-31 | PXD051849 | Pride

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