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Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE139058 | GEO | 2020/04/30

REPOSITORIES: GEO

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Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [RNA-seq]

Project description:The goal of this study is to determine the capacity of Tcf1 to reprogram exhausted CD8+ T cells for function restoration. Tex cells elicited by chronic infection contain a CXCR5+Tim3– subset that has stem cell-like self-renewing capacity and expresses an elevated level of Tcf1 (termed Tex-stem), and Tex-stem cells depend on Tcf1 for generation and persistence. We show that ectopic Tcf1 expression profoundly affected the transcriptome of Tex cells.

2020-04-30 | GSE139057 | GEO

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [CUT&RUN]

2020-04-30 | GSE139056 | GEO

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [ATAC-seq]

2020-04-30 | GSE139024 | GEO

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features

Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features

| PRJNA578159 | ENA

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [RNA-seq]

Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [RNA-seq]

| PRJNA578161 | ENA

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [CUT&RUN]

Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [CUT&RUN]

| PRJNA578160 | ENA

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [ATAC-seq]

Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [ATAC-seq]

| PRJNA578114 | ENA

Ectopic Tcf1 expression instills a stem-like program in exhausted CD8<sup>+</sup> T cells to enhance viral and tumor immunity.

Project description:Exhausted CD8+ T (Tex) cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts. A stem cell-like Tex (Tex-stem) subset can self-renew and differentiate into terminally exhausted (Tex-term) cells. Here, we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor models. Tcf1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade, leading to enhanced viral and tumor control. Mechanistically, ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells, such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes, including Mx1, Tox2, and Runx3. These findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.

| S-EPMC8093427 | biostudies-literature

NR4a1/2 deletion promotes accumulation of TCF1+ stem-like precursors of exhausted CD8+ T cells in the tumor microenvironment

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

2024-02-01 | GSE242056 | GEO

The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection.

Project description:The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

| S-EPMC6381939 | biostudies-literature

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