Evidence map›Paper›PMID 39673127›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-β signal.

Shen Zheng, Xuan Che, Kai Zhang, Yun Bai, Hongkui Deng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

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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

5 authors.

Shen ZhengDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking University, Beijing 100191, China.
Xuan CheDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking University, Beijing 100191, China.
Kai ZhangDepartment of Dermatology and Venerology, Peking University First Hospital, National Clinical Research Center for Skin and Immune Diseases, Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Peking University, Beijing, China; Institute of Advanced Clinical Medicine, Peking University, Beijing, China.
Yun BaiDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking University, Beijing 100191, China. Electronic address: baiyun@bjmu.edu.cn.
Hongkui DengDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking University, Beijing 100191, China; MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address: hongkui_deng@pku.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The immunosuppressive tumor microenvironment represents a key challenge for chimeric antigen receptor (CAR) T cells in solid tumors and includes the production of the inhibitory cytokine transforming growth factor β (TGF-β), which limits CAR-T cell persistence and function. Current strategies involving the blockade of TGF-β signaling have little benefit for solid tumor treatment. Here, we demonstrate a novel inverted cytokine receptor (ICR)-modified CAR-T cell strategy not only TGF-β signal blockade but also antitumor efficacy enhancement. The newly designed T cells carry an ICR construct that fuses the TGF-β receptor II extracellular domain to the interleukin-15 (IL-15) receptor α cytoplasmic domain (named TB15) and is directed to the tumor antigen epidermal growth factor receptor by a CAR construct. In mice with high TGF-β solid tumors, our signal-inverted CAR/TB15 T cells effectively treat tumors by blocking TGF-β and repurposing IL-15 stimulative signaling, resulting in enhanced CAR-T cell persistence and function. As a proof of concept, our study results extend synthetic receptor signaling beyond CAR-directed killing, which could endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumors by using a chimeric ICR.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenSignal TransductionT-LymphocytesTransforming Growth Factor betaTumor MicroenvironmentAnimalsCell Line, TumorDisease Models, AnimalHumansInterleukin-15MiceReceptors, Transforming Growth Factor betaXenograft Model Antitumor AssaysInterleukin-15Receptors, Chimeric AntigenReceptors, Transforming Growth Factor betaTransforming Growth Factor betaCAR-T cellsimmunosuppressive tumor microenvironmentinterleukin-15inverted cytokine receptorstransforming growth factor β

Identifiers

PMID39673127
PMCPMC11853376

What OpenQuestion holds

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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.