Evidence map›Paper›PMID 42839060›Full record

ArticleNature cancer2026

Intestinal epithelial GSK3β governs fumarate-dependent neutrophil reprogramming to promote colorectal cancer.

Xiao-Shun He, Xiao-Qin Yang, Shan Wan, Yun Yang, Wen-Juan Gan, Yi-Xuan Liu, Zu-Da Pan, Hai-Yi Zhang, Kuang He, Xin Guo and 11 more

Abstract read
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In one paragraph

Article in Nature cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Xiao-Shun He *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Xiao-Qin Yang *Department of Bioinformatics, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.ORCID http://orcid.org/0000-0002-9539-2785
Shan Wan *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Yun Yang *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.ORCID http://orcid.org/0000-0003-2311-0598
Wen-Juan Gan *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.ORCID http://orcid.org/0000-0002-0436-1028
Yi-Xuan Liu *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Zu-Da Pan *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Hai-Yi Zhang *Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Kuang HeDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Xin GuoDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Juan LiuDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Zhi JiangNational Center of Technology Innovation for Biopharmaceuticals, Suzhou Biomedical Industry Innovation Center, Suzhou, China.
Wen-Xin WuDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Feng LiuDepartment of General Surgery, Suzhou Guangci Cancer Hospital, Suzhou, China.ORCID http://orcid.org/0000-0002-3121-5210
Yue-Yue WuDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Yuan-Meng HuDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Ruo-Yang ZhangDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Shuo JiangDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Wei-Wei SunDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Yan-Ru WangDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Hua WuDepartment of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China. wuhua@suda.edu.cn.ORCID http://orcid.org/0000-0002-4210-2377

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82022050National Natural Science Foundation of China (National Science Foundation of China) 82372662National Natural Science Foundation of China (National Science Foundation of China) 82373142Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation) BE2023703Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation) BG2025055
6 · The paper itself

Abstract

Tumor-infiltrating neutrophils (TINs) promote colorectal cancer progression and therapeutic resistance, but their reprogramming mechanisms remain unclear. Using mouse models and multiomics profiling, we reveal that intestinal epithelial glycogen synthase kinase-3-β (GSK3β) orchestrates fumarate-dependent TIN polarization. GSK3β-primed T3 neutrophils express FTH1 and PD-L1, conferring ferroptosis resistance and immune evasion. Mechanistically, nuclear GSK3β phosphorylates linker histone H1FX, triggering its proteasomal degradation via USP43 dissociation and elevating chromatin accessibility for glycolytic gene transcription. Lactate inactivates fumarate hydratase through lactylation, driving intratumoral fumarate accumulation. Fumarate inhibits KDM2B activity in TINs, elevating histone H3 lysine 36 dimethylation to trigger epigenetic reprogramming toward immunosuppressive T3 neutrophils. Pharmacological GSK3β inhibition with tideglusib attenuates T3 polarization and potentiates checkpoint blockade in preclinical colorectal cancer models. Our work establishes a metabolic-epigenetic axis controlling TIN reprogramming and suggests combinatorial immunotherapies for CRC.

Identifiers

PMID42839060

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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 OpenQuestion graph.