Evidence map›Paper›PMID 35017664›Full record

ArticleOncogene2022

Blockade of beta-adrenergic receptors reduces cancer growth and enhances the response to anti-CTLA4 therapy by modulating the tumor microenvironment.

Klaire Yixin Fjæstad, Anne Mette Askehøj Rømer, Victor Goitea, Astrid Zedlitz Johansen, Marie-Louise Thorseth, Marco Carretta, Lars Henning Engelholm, Lars Grøntved, Niels Junker, Daniel Hargbøl Madsen

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
16.7field-weighted citation impact, top 1% of its field
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

104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.

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44 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 1 country.

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
Anne Mette Askehøj RømerNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Victor GoiteaDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Astrid Zedlitz JohansenNational 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.
Marco CarrettaNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Lars Henning EngelholmFinsen Laboratory, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Lars GrøntvedDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Niels Junker *Department of Oncology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Daniel Hargbøl Madsen *National 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
University of Copenhagen · DKHerlev Hospital · DKUniversity of Southern Denmark · DKGentofte Hospital · DKRoskilde University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The development of immune checkpoint inhibitors (ICI) marks an important breakthrough of cancer therapies in the past years. However, only a limited fraction of patients benefit from such treatments, prompting the search for immune modulating agents that can improve the therapeutic efficacy. The nonselective beta blocker, propranolol, which for decades has been prescribed for the treatment of cardiovascular conditions, has recently been used successfully to treat metastatic angiosarcoma. These results have led to an orphan drug designation by the European Medicines Agency for the treatment of soft tissue sarcomas. The anti-tumor effects of propranolol are suggested to involve the reduction of cancer cell proliferation as well as angiogenesis. Here, we show that oral administration of propranolol delays tumor progression of MCA205 fibrosarcoma model and MC38 colon cancer model and increases the survival rate of tumor bearing mice. Propranolol works by reducing tumor angiogenesis and facilitating an anti-tumoral microenvironment with increased T cell infiltration and reduced infiltration of myeloid-derived suppressor cells (MDSCs). Using T cell deficient mice, we demonstrate that the full anti-tumor effect of propranolol requires the presence of T cells. Flow cytometry-based analysis and RNA sequencing of FACS-sorted cells show that propranolol treatment leads to an upregulation of PD-L1 on tumor associated macrophages (TAMs) and changes in their chemokine expression profile. Lastly, we observe that the co-administration of propranolol significantly enhances the efficacy of anti-CTLA4 therapy. Our results identify propranolol as an immune modulating agent, which can improve immune checkpoint inhibitor therapies in soft tissue sarcoma patients and potentially in other cancers.

Identifiers

PMID35017664
PMCPMC8881216
OpenAlexW4206697973

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.