Evidence map›Paper›PMID 41364522›Full record

ArticleThe Journal of clinical investigation2026

A fungi-derived cyclic peptide enhances Th9-mediated antitumor immunity by targeting ZAP70 and SREBP1.

Wenli Zhao, Yang Zhou, Yuyang Chen, Yicheng Sun, Jiaxin Tang, Yihan Zhu, Jie Ren, Tianxu Du, Handuo Wang, Yuan Gao and 5 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. FOXP1 Knockdown Reprograms Th9 CAR-T Cells to Overcome Antigen Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. 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

15 authors.

Wenli ZhaoDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Yang ZhouDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Yuyang ChenDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Yicheng SunDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Jiaxin TangDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yihan ZhuDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Jie RenDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Tianxu DuDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Handuo WangDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Yuan GaoDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
Yu HuDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-organ Injury Prevention and Treatment, National Clinical Research Center for Kidney Disease, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, Guangdong, China.
Ling JiangDepartment of Hematology, Nanfang Hospital, and.
Tomohiko OhwadaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Qi LuoSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Enguang BiDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adoptive cell therapy (ACT) relies on durable and functional T cells to mediate tumor clearance. Th9 cells are a metabolically fit CD4+ T cell subset with strong persistence but limited cytotoxicity. Here, we identified endomelipeptide A (EpA), a cyclic peptide isolated from Ganoderma lucidum-associated endophytic fungi, as a potent enhancer of Th9 cell differentiation. EpA promoted a cytotoxic Th9 phenotype with enhanced mitochondrial function and metabolic fitness. Mechanistically, EpA dually targeted ZAP70 and SREBP1, coupling T cell receptor signaling activation with lipid metabolism suppression. EpA-treated Th9 cells mediated robust, CD8+ T cell-dependent tumor control and enhanced the efficacy of human Th9 CAR T cell therapy in vivo. These findings establish EpA as a distinct cyclic peptide that reprograms Th9 cells and provides a potential approach to boost ACT efficacy.

Indexed as

Immunotherapy, AdoptiveNeoplasm ProteinsPeptides, CyclicSterol Regulatory Element Binding Protein 1T-Lymphocytes, Helper-InducerZAP-70 Protein-Tyrosine KinaseAnimalsCD8-Positive T-LymphocytesCell Line, TumorHumansMiceNeoplasm ProteinsPeptides, CyclicSterol Regulatory Element Binding Protein 1ZAP-70 Protein-Tyrosine KinaseCancer immunotherapyImmunologyOncologyPeptidesT cells

Identifiers

PMID41364522
PMCPMC12867150

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Registered trials

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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.