Evidence map›Paper›PMID 39879981›Full record

ArticleCell metabolism2025

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy.

Andrew T Frisch, Yiyang Wang, Bingxian Xie, Aaron Yang, B Rhodes Ford, Supriya Joshi, Katarzyna M Kedziora, Ronal Peralta, Drew Wilfahrt, Steven J Mullett and 9 more

Abstract read
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Review
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  4. Article
  5. Review
  6. DADA Enhances CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. The pyruvate branch point controls lymphoid cancer cell dissemination.bioRxiv : the preprint server for biology · 2026
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Regulators of CD8Nature reviews. Immunology · 2026
    Review
  16. Review
  17. TMEM33 deletion potentiates anti-tumor CD8bioRxiv : the preprint server for biology · 2026
    Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Andrew T FrischDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Yiyang WangDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tsinghua University, Beijing, China.
Bingxian XieDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Aaron YangDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, UPMC Children's Hospital, Pittsburgh, PA, USA.
B Rhodes FordDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, UPMC Children's Hospital, Pittsburgh, PA, USA.
Supriya JoshiDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Katarzyna M KedzioraDepartment of Cell Biology, Center for Biologic Imaging (CBI), University of Pittsburgh, Pittsburgh, PA, USA.
Ronal PeraltaDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Drew WilfahrtDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Steven J MullettDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Kellie SpahrDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Konstantinos LontosDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Jessica A JanaDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Victoria G DeanDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
William G GunnDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Stacy GelhausDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Amanda C PoholekDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, UPMC Children's Hospital, Pittsburgh, PA, USA.
Dayana B RivadeneiraDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Greg M DelgoffeDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: gdelgoffe@pitt.edu.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dan Paul Zandberg · 1988 to 2026
$158.0M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Uncovering the metabolic underpinnings of T cell exhaustionR01AI166598 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2022 to 2025
$3.2M
Dissecting the role of hypoxia in T cell differentiation in cancerR01CA277473 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Greg M. Delgoffe, Yana Najjar · 2023 to 2026
$2.4M
Metabolic control of regulatory T cell functional identityR01AI171483 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2022 to 2025
$2.4M
Exploring and exploiting metabolic plasticity in regulatory T cellsDP2AI136598 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2017 to 2017
$2.3M
An Exploris 240 for MetabolomicsS10OD032141 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GELHAUS, STACY LYNN · 2022 to 2022
$600k
Metabolically improving the generation, function, and persistence of therapeutic T cells for the treatment of cancerF31CA257760 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRISCH, ANDREW · 2021 to 2022
$93k
NCI NIH HHS F31 CA257760NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA277473NCI NIH HHS T32 CA082084NIAID NIH HHS DP2 AI136598NIAID NIH HHS R01 AI166598NIAID NIH HHS R01 AI171483NIH HHS S10 OD032141
6 · The paper itself

Abstract

Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo. We used dichloroacetate (DCA) to modulate glycolytic metabolism during expansion, resulting in elevated mitochondrial capacity, stemness, and improved antitumor efficacy in murine T cell receptor (TCR)-Tg and human CAR-T cells. DCA-conditioned T cells surprisingly show no elevated intratumoral effector function but rather have improved engraftment. DCA conditioning decreases reliance on glucose, promoting usage of serum-prevalent physiologic carbon sources. Further, DCA conditioning promotes metabolic flux from mitochondria to chromatin, resulting in increased histone acetylation at key longevity genes. Thus, hyperglycemic culture conditions promote expansion at the expense of metabolic flexibility and suggest pharmacologic metabolic rewiring as a beneficial strategy for improvement of cellular immunotherapies.

Indexed as

Epigenesis, GeneticGlucoseImmunotherapyNeoplasmsT-LymphocytesAnimalsCell Line, TumorCell ProliferationDichloroacetic AcidGlycolysisHumansImmunotherapy, AdoptiveMiceMice, Inbred C57BLMitochondriaDichloroacetic AcidGlucoseCAR-Tcell therapyepigeneticsglucoseImmunometabolismimmunotherapylongevitymetabolismmitochondriaT cell

Identifiers

PMID39879981
PMCPMC12101091

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.