Evidence map›Paper›PMID 41249783›Full record

ArticleNature communications2025

β-adrenergic signaling blockade attenuates metastasis through activation of cytotoxic CD4 T cells.

Klaire Yixin Fjæstad, Astrid Zedlitz Johansen, Hannes Linder, Kevin James Baker, Milou Schattefor, Nadia Kolvig Czajkowski, Marie-Louise Thorseth, Majken Siersbæk, Annina Kurzay, Maria Perez-Penco and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
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  8. 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

19 authors.

Klaire Yixin FjæstadNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0002-0141-6898
Astrid Zedlitz JohansenNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0002-4948-6799
Hannes LinderNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Kevin James BakerNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Milou SchatteforNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Nadia Kolvig CzajkowskiNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Marie-Louise ThorsethNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Majken SiersbækDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0003-1030-182X
Annina KurzayNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0001-5388-6827
Maria Perez-PencoNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Anne RahbechNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Sara Fresnillo SalóNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0009-0002-6869-7337
Lars Henning EngelholmFinsen Laboratory, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Inge Marie SvaneNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0002-9451-6037
Mads Hald AndersenNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0002-2914-9605
Niels JunkerDepartment of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.ORCID http://orcid.org/0000-0001-8348-9363
Lars GrøntvedDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0002-6735-8483
Per Thor StratenNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Daniel Hargbøl MadsenNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark. daniel.hargboel.madsen@regionh.dk.ORCID http://orcid.org/0000-0002-3183-6201

Funding

Kræftens Bekæmpelse (Danish Cancer Society) R311-A18254Lundbeckfonden (Lundbeck Foundation) R307-2018-3326
6 · The paper itself

Abstract

β-adrenergic signaling has been suggested to promote tumor growth, and β-blockers are being evaluated for repurposing for cancer treatment. Here, we identify a β-adrenergic signaling axis involved in metastasis formation. We show that the β-blocker propranolol has strong anti-metastatic activity in multiple murine models, with this effect being completely dependent on CD4 + T cells and independent of NK or CD8 + T cells. We also observe that CD4 + T cells are required for the anti-tumor effect of propranolol in a syngeneic subcutaneous model of colon cancer. Mechanistically, propranolol induces a Th1-polarized and cytotoxic CD4 + T cell response, which requires MHC class II expression by cancer cells for full efficacy. We also report propanolol-driven systemic changes in the monocyte compartment, and upon depletion of monocytes, propranolol loses its anti-tumor effects. Finally, we show that propranolol treatment synergizes with anti-CTLA-4 therapy to further enhance CD4 + T cell infiltration and control metastasis. Thus, we show that β-adrenergic signaling limits CD4 T cell-mediated anti-tumor immunity, highlighting the potential of repurposing β-blockers for cancer treatment.

Indexed as

Adrenergic beta-AntagonistsCD4-Positive T-LymphocytesColonic NeoplasmsPropranololT-Lymphocytes, CytotoxicAnimalsCD8-Positive T-LymphocytesCell Line, TumorCTLA-4 AntigenFemaleHumansLymphocyte ActivationMiceMice, Inbred C57BLMonocytesNeoplasm MetastasisAdrenergic beta-AntagonistsCTLA-4 AntigenPropranololReceptors, Adrenergic, beta

Identifiers

PMID41249783
PMCPMC12623787

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.