Evidence map›Paper›PMID 40759573›Full record

ArticleThe Journal of clinical investigation2025

A CD4+ T lymphocyte-specific TCR/GSDMD/IL-2 axis facilitates antitumor immunity.

Yihan Yao, Lingling Wang, Weiqin Jiang, Ning Wang, Mengjie Li, Wenlong Lin, Ting Zhang, Wanqiang Sheng, Xiaojian Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  3. 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

9 authors.

Yihan YaoInstitute of Immunology and Bone Marrow Transplantation Center and.
Lingling WangInstitute of Immunology and Bone Marrow Transplantation Center and.
Weiqin JiangDepartment of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Ning WangInstitute of Immunology and Bone Marrow Transplantation Center and.
Mengjie LiInstitute of Immunology and Bone Marrow Transplantation Center and.
Wenlong LinInstitute of Immunology and Bone Marrow Transplantation Center and.
Ting ZhangDepartment of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Wanqiang ShengInstitute of Immunology and Department of Respiratory Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiaojian WangInstitute of Immunology and Bone Marrow Transplantation Center and.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gasdermin (GSDM) family proteins mediate tumor pyroptosis and impact cancer progression, but other than that, their involvement in the tumor immune microenvironment remains largely unknown. Here, we show that activation of GSDMD in human tumor specimens mainly occurs in tumor-infiltrating leukocytes. Significantly, GSDMD deficiency or its inactivation in CD4+ T cells disabled CD8+ T cell-mediated antitumor immunity and caused tumor outgrowth in mice. Further study uncovered that, via inducing IL-2 production, GSDMD was required for CD4+ T cells to provide help to CD8+ T cell function. Mechanistically, GSDMD was cleaved by TCR stimulation-activated caspase-8 to form GSDMD-N pores, which enhanced Ca2+ influx for IL-2 induction. Moreover, GSDMD activation and function were conserved in human CD4+ T cells and associated with favorable prognosis and improved response to anti-PD-1 immunotherapy in colonic and pancreatic cancer. We believe this study identifies a new nonpyroptotic role of GSDMD in tumor immunity, proposing GSDMD as a potential target for cancer immunotherapy.

Indexed as

CD4-Positive T-LymphocytesColonic NeoplasmsInterleukin-2Intracellular Signaling Peptides and ProteinsNeoplasm ProteinsNeoplasmsPancreatic NeoplasmsPhosphate-Binding ProteinsReceptors, Antigen, T-CellAnimalsCD8-Positive T-LymphocytesCell Line, TumorGasderminsHumansLymphocytes, Tumor-InfiltratingMiceGasderminsGSDMD protein, humanGsdmd protein, mouseIL2 protein, humanInterleukin-2Intracellular Signaling Peptides and ProteinsNeoplasm ProteinsPhosphate-Binding ProteinsReceptors, Antigen, T-CellCalcium signalingCancer immunotherapyImmunologyOncologyT cells

Identifiers

PMID40759573
PMCPMC12321394

What OpenQuestion holds

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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 OpenQuestion graph.