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Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies

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

ORGANISM(S): Mus musculus

PROVIDER: GSE249771 | GEO | 2025/05/30

REPOSITORIES: GEO

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Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (RNA-Seq)

Project description:Cellular therapies are uniquely living drugs that must survive and persist within the body to achieve anti-tumor efficacy. In vitro culture of therapeutic T cells often relies on hypermetabolic conditions to maximize expansion. We show that this non-physiologic environment generates metabolically and functionally impaired T cells that more readily rely on aerobic glycolysis than T cells found in vivo. To target this shift in glycolytic metabolism, we employ dichloroacetate (DCA) during in vitro expansion resulting in elevated mitochondrial capacity and stemness properties pre-infusion - ultimately improving anti-tumor efficacy. DCA-conditioned T cells surprisingly show no elevated intratumoral function, but have an immediate and long-term survival benefit. DCA conditioning decreases reliance on extracellular glucose by promoting the usage of more physiologic carbon sources. This metabolic shift increases histone acetylation at key longevity genes dependent on citrate export from mitochondria. Blockade of mitochondrial citrate export – and thus formation of cytosolic acetyl-coA – reverses the beneficial effects of DCA. Our data suggest a simple means of correcting in vitro expansion of adoptive cell therapies for enhanced anti-tumor efficacy.

2025-05-30 | GSE249770 | GEO

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (CUT&Tag)

2025-05-30 | GSE249769 | GEO

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (ATAC-Seq)

2025-05-30 | GSE249768 | GEO

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies

Project description:Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies

| PRJNA1050304 | ENA

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (RNA-Seq)

Project description:Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (RNA-Seq)

| PRJNA1050307 | ENA

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (ATAC-Seq)

Project description:Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (ATAC-Seq)

| PRJNA1050306 | ENA

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (CUT&Tag)

Project description:Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior anti-tumor T cells for adoptive cell therapies (CUT&Tag)

| PRJNA1050305 | ENA

Limiting metabolic stress by redirecting glucose flux during in vitro expansion improves efficacy of T cell therapies for cancer

Project description:Adoptive cell therapies for cancer treatment often fail due to a lack of T cell survival and persistence within the patient. Redirecting glycolytic processing with dichloroacetate (DCA) during in vitro expansion improves immediate and long-term T cell engraftment by up to 8x - ultimately resulting in a drastic improvement in tumor clearance. Here we use bulk RNA sequencing to interrogate the changes in transcriptional programs resultant of DCA treatment that may confer the observed improvement in engraftment and tumor clearance of DCA-treated T cells.

2023-11-01 | GSE216666 | GEO

Limiting metabolic stress by redirecting glucose flux during in vitro expansion improves efficacy of T cell therapies for cancer

Project description:Limiting metabolic stress by redirecting glucose flux during in vitro expansion improves efficacy of T cell therapies for cancer

| PRJNA894722 | ENA

Redirecting the immune response: role of adoptive T cell therapy.

Project description:Adoptive T cell therapy is aimed at overcoming constraints of the endogenous immune response. In patients with malignancies, this approach is based on the possibility of administering sufficient numbers of tumor-reactive lymphocytes under conditions in which they will promote a therapeutic response. Although this strategy is potentially applicable to a vast number of malignancies, its efficacy, to date, has been limited. This is likely related to several factors including an insufficient persistence and reactivation of infused cells, insufficient tumor infiltration, and the presence of an immunosuppressive environment. Here, we review the importance of pretransplantation host conditioning and posttransplantation strategies that have been shown to contribute to the therapeutic efficacy of infused T lymphocytes.

| S-EPMC2938351 | biostudies-literature

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