Evidence map›Paper›PMID 39482885›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Inhibition of Glutamate-to-Glutathione Flux Promotes Tumor Antigen Presentation in Colorectal Cancer Cells.

Tao Yu, Kevin Van der Jeught, Haiqi Zhu, Zhuolong Zhou, Samantha Sharma, Sheng Liu, Haniyeh Eyvani, Ka Man So, Naresh Singh, Jia Wang and 7 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. ALDH1L1 reverses CD8Journal of translational medicine · 2026
    Article
  6. Review
  7. Review
  8. Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. 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

17 authors.

Tao YuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-1903-7589
Kevin Van der JeughtDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Haiqi ZhuCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Zhuolong ZhouDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Samantha SharmaDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Haniyeh EyvaniDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Ka Man SoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Naresh SinghDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Jia WangCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
George E SanduskyDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Yunlong LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Mateusz OpyrchalMelvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sha CaoMelvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Chi ZhangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Xinna ZhangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0003-4118-2245

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Development of data driven and AI empowered systems biology to study human diseasesR35GM150971 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Chi Zhang · 2023 to 2026
$1.6M
American Cancer Society RSG-22-062-01-MMIndiana Clinical and Translational Sciences InstituteMelvin and Bren Simon Cancer Center, Indiana UniversityNational Science Foundation DBI-2047631NCI NIH HHS P30 CA082709NIGMS NIH HHS 1R35GM150971NIGMS NIH HHS R35 GM150971
6 · The paper itself

Abstract

Colorectal cancer (CRC) cells display remarkable adaptability, orchestrating metabolic changes that confer growth advantages, pro-tumor microenvironment, and therapeutic resistance. One such metabolic change occurs in glutamine metabolism. Colorectal tumors with high glutaminase (GLS) expression exhibited reduced T cell infiltration and cytotoxicity, leading to poor clinical outcomes. However, depletion of GLS in CRC cells has minimal effect on tumor growth in immunocompromised mice. By contrast, remarkable inhibition of tumor growth is observed in immunocompetent mice when GLS is knocked down. It is found that GLS knockdown in CRC cells enhanced the cytotoxicity of tumor-specific T cells. Furthermore, the single-cell flux estimation analysis (scFEA) of glutamine metabolism revealed that glutamate-to-glutathione (Glu-GSH) flux, downstream of GLS, rather than Glu-to-2-oxoglutarate flux plays a key role in regulating the immune response of CRC cells in the tumor. Mechanistically, inhibition of the Glu-GSH flux activated reactive oxygen species (ROS)-related signaling pathways in tumor cells, thereby increasing the tumor immunogenicity by promoting the activity of the immunoproteasome. The combinatorial therapy of Glu-GSH flux inhibitor and anti-PD-1 antibody exhibited a superior tumor growth inhibitory effect compared to either monotherapy. Taken together, the study provides the first evidence pointing to Glu-GSH flux as a potential therapeutic target for CRC immunotherapy.

Indexed as

Colorectal NeoplasmsGlutamic AcidGlutathioneAnimalsAntigen PresentationCell Line, TumorDisease Models, AnimalGlutaminaseHumansMiceTumor MicroenvironmentGlutamic AcidGlutaminaseGlutathionecolorectal cancerglutamine metabolismimmune checkpoint blockadeimmunoproteasomeMHC‐I antigen presentationsingle‐cell flux estimation analysis

Identifiers

PMID39482885
PMCPMC11714253

What Socratic holds

Textmetadata
LicenceCC BY
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.