Evidence map›Paper›PMID 40234680›Full record

ArticleNature cancer2025

Overcoming extracellular vesicle-mediated fratricide improves CAR T cell treatment against solid tumors.

Wenqun Zhong, Zhiyuan Qin, Ziyan Yu, Jingbo Yang, Dongdong Yan, Nils W Engel, Neil C Sheppard, Yi Fan, Ravi Radhakrishnan, Xiaowei Xu and 4 more

Abstract read
In one paragraph

Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. PD-L1Biomarker research · 2026
    Article
  5. Article
  6. Review
  7. Trogocytosis in cancer immunity and cellular immunotherapy: mechanisms, therapeutic challenges, and translational opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  8. Review
  9. Article
  10. Review
  11. 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

14 authors.

Wenqun ZhongDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Zhiyuan QinDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Ziyan YuDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Jingbo YangDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Dongdong YanCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nils W EngelCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Neil C SheppardCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yi FanDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Ravi RadhakrishnanDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
Xiaowei XuDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4098-7690
Leyuan MaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Serge Y FuchsDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0136-5103
Carl H JuneCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0241-3557
Wei GuoDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. guowei@sas.upenn.edu.ORCID http://orcid.org/0000-0002-9251-0360

Funding

Molecular Basis and Regulatory Mechanisms of Exosome SecretionR35GM141832 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WEI GUO · 2021 to 2026
$3.9M
Targeting immunosuppression of intratumoral CAR T cellsR01CA285321 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Michael S Cohen, Serge Y Fuchs · 2024 to 2026
$1.5M
NCI NIH HHS R01 CA285321NIGMS NIH HHS R35 GM141832U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM141832
6 · The paper itself

Abstract

The efficacy of chimeric antigen receptor (CAR) T cells against solid tumors is limited. The molecular mechanisms underlying CAR T cell resistance are yet to be elucidated and new strategies need to be developed to improve treatment outcomes. Here we report that solid tumors respond to CAR T cells by upregulating the secretion of small extracellular vesicles carrying tumor antigens, which are horizontally transferred to CAR T cells, leading to antigen recognition and CAR T cell fratricide. Engineered CAR T cells armored with Serpin B9, a major granzyme B inhibitor, show decreased fratricide and increased vitality, tumor infiltration, and antitumor activity in female mice. Moreover, Serpin B9-armored CAR T cells show higher efficacy than parental CAR T cells in treating solid tumors when combined with the anti-programmed death 1 antibody. Our study demonstrates a mechanism that limits CAR T cell function and suggests an improved strategy in tumor treatment.

Indexed as

Extracellular VesiclesImmunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenT-LymphocytesAnimalsAntigens, NeoplasmCell Line, TumorFemaleGranzymesHumansMiceSerpinsXenograft Model Antitumor AssaysAntigens, NeoplasmGranzymesReceptors, Chimeric AntigenSerpins

Identifiers

PMID40234680
PMCPMC12303731

What OpenQuestion holds

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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 OpenQuestion graph.