Evidence map›Paper›PMID 36854895›Full record

ArticleCancer gene therapy2023

β3-adrenergic receptor on tumor-infiltrating lymphocytes sustains IFN-γ-dependent PD-L1 expression and impairs anti-tumor immunity in neuroblastoma.

Gennaro Bruno, Nicoletta Nastasi, Angela Subbiani, Alessia Boaretto, Sara Ciullini Mannurita, Gianluca Mattei, Patrizia Nardini, Chiara Della Bella, Alberto Magi, Alessandro Pini and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

19 citing papers in PubMed, 18 citations in OpenAlex.

  1. Circulating Beta3-Adrenoreceptor as Novel Independent Biomarker for Risk Assessment in Neuroblastoma Patients.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Review
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  4. Article
  5. A BBB-permeable βScience advances · 2026
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  8. Article
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  11. Targeting nerve growth factor: an Achilles' heel for tumors?Journal for immunotherapy of cancer · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. β-Adrenoceptors in Cancer: Old Players and New Perspectives.Handbook of experimental pharmacology · 2024
    Review
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  17. Article
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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 at 3 institutions in 1 country.

Gennaro BrunoDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy. gennaro.bruno@unifi.it.ORCID 0000-0001-6252-3825
Nicoletta NastasiDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Angela SubbianiDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Alessia BoarettoDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Sara Ciullini MannuritaDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Gianluca MatteiDepartment of Information Engineering, University of Florence, Florence, Italy.
Patrizia NardiniDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Chiara Della BellaDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Alberto MagiDepartment of Information Engineering, University of Florence, Florence, Italy.
Alessandro PiniDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Emanuela De MarcoPediatric Hematology and Oncology, University Hospital of Pisa, Pisa, Italy.
Annalisa TondoDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Claudio FavreDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Maura CalvaniDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Meyer Children's Hospital · ITUniversity of Florence · ITAzienda Ospedaliera Universitaria Pisana · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via β-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.

Indexed as

Interferon-gammaNeuroblastomaAnimalsB7-H1 AntigenHumansLymphocytes, Tumor-InfiltratingMiceReceptors, Adrenergic, beta-3Tumor MicroenvironmentADRB3 protein, humanB7-H1 AntigenInterferon-gammaReceptors, Adrenergic, beta-3

Identifiers

PMID36854895
PMCPMC10281870
OpenAlexW4322718815

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Registered trials

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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.