Evidence map›Paper›PMID 39478186›Full record

ArticleNPJ precision oncology2024

CCL3 predicts exceptional response to TGFβ inhibition in basal-like pancreatic cancer enriched in LIF-producing macrophages.

Silvia Pietrobono, Monica Bertolini, Veronica De Vita, Fabio Sabbadini, Federica Fazzini, Cristina Frusteri, Enza Scarlato, Domenico Mangiameli, Alberto Quinzii, Simona Casalino and 3 more

Erratum issuedAbstract read
In one paragraph

Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Trial
  2. Article
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  6. Review
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  8. Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Silvia Pietrobono *Department of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Monica Bertolini *Department of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Veronica De VitaDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Fabio SabbadiniDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Federica FazziniInvestigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Cristina FrusteriDepartment of Engineering for Innovation Medicine, University of Verona, Verona, Italy.
Enza ScarlatoDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Domenico MangiameliDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Alberto QuinziiDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Simona CasalinoDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Camilla ZecchettoDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Valeria MerzDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.
Davide MelisiDepartment of Medicine, Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy. davide.melisi@univr.it.ORCID http://orcid.org/0000-0002-4031-7585

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 23719
6 · The paper itself

Abstract

The TGFβ receptor inhibitor galunisertib showed promising efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the phase 2 H9H-MC-JBAJ study. Identifying biomarkers for this treatment remains essential. Baseline plasma levels of chemokine CCL3 were integrated with clinical outcomes in PDAC patients treated with galunisertib plus gemcitabine (n = 104) or placebo plus gemcitabine (n = 52). High CCL3 was a poor prognostic factor in the placebo group (mOS 3.6 vs. 10.1 months; p < 0.01) but a positive predictor for galunisertib (mOS 9.2 vs. 3.6 months; p < 0.01). Mechanistically, tumor-derived CCL3 activates Tgfβ signaling in macrophages, inducing their M2 phenotype and Lif secretion, sustaining a mesenchymal/basal-like ecotype. TGFβ inhibition redirects macrophage polarization to M1, reducing Lif and shifting PDAC cells to a more epithelial/classical phenotype, improving gemcitabine sensitivity. This study supports exploring TGFβ-targeting agents in PDAC with a mesenchymal/basal-like ecotype driven by high CCL3 levels.

Identifiers

PMID39478186
PMCPMC11525688

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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.