Evidence map›Paper›PMID 41364531›Full record

ArticleJCI insight2026

Nectin-4 reduces T cell effector function and is a therapeutic target in pancreatic cancer.

Max Heiduk, Carolin Beer, Sarah Cronjaeger, Emily A Kawaler, Ulrich Sommer, Franziska Baenke, David Digomann, Loreen Natusch Bufe, Charlotte Reiche, Jessica Glück and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. 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. TIGITCancers · 2026
    Article
  2. Review
  3. Article
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

17 authors.

Max HeidukDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Carolin BeerDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Sarah CronjaegerDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Emily A KawalerPerlmutter Cancer Center, NYU Langone Health, New York, New York, USA.
Ulrich SommerInstitute of Pathology, Faculty of Medicine Carl Gustav Carus, and.
Franziska BaenkeDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
David DigomannDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Loreen Natusch BufeDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Charlotte ReicheDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Jessica GlückDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Franziska HoffmannDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Sungsik KimDepartment of Surgery, Moores Cancer Center, UC San Diego Health, San Diego, California, USA.
Daniel E StangeDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Diane M SimeoneDepartment of Surgery, Moores Cancer Center, UC San Diego Health, San Diego, California, USA.
Jürgen WeitzDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Lena SeifertDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Adrian M SeifertDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and current therapies show limited efficacy. Ligands and receptors of the TIGIT axis were analyzed using multicolor flow cytometry of tumor and blood samples, IHC from primary tumors, and single-cell RNA-Seq from primary tumors and liver metastasis from patients with various stages of PDAC. The effect of soluble and plate-bound Nectin-4 on T cell function was tested in vitro. Furthermore, patient-derived PDAC organoids were treated with the standard-of-care therapies FOLFIRINOX, gemcitabine plus paclitaxel, or the antibody-drug conjugate enfortumab vedotin. TIGIT expression was increased on tumor-infiltrating conventional T cells and Tregs compared with T cells from matched blood. Nectin-4 but not CD155 expression was associated with poor outcome. Nectin-4 was exclusively expressed by tumor cells and correlated with low immune infiltration. Notably, Nectin-4 inhibited T cell effector cytokine production in vitro. Targeting Nectin-4 with the antibody-drug conjugate enfortumab vedotin inhibited tumor growth in multiple patient-derived PDAC organoids. Collectively, our data underscore Nectin-4 as a potential novel therapeutic target and provide the rationale to test this agent in patients with PDAC.

Indexed as

Carcinoma, Pancreatic DuctalCell Adhesion MoleculesPancreatic NeoplasmsT-LymphocytesAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorDeoxycytidineFemaleGemcitabineHumansLeucovorinLymphocytes, Tumor-InfiltratingMaleMiceNectinsCell Adhesion MoleculesDeoxycytidineGemcitabineLeucovorinNECTIN4 protein, humanNectinsOxaliplatinPaclitaxelReceptors, ImmunologicTIGIT protein, humanCancerGastroenterologyOncologyT cells

Identifiers

PMID41364531
PMCPMC12892910

What Socratic holds

Textmetadata
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 Socratic graph.