Evidence map›Paper›PMID 41372751›Full record

ArticleBreast cancer research : BCR2025

Modelling the metastatic immune microenvironment in triple-negative breast cancer.

Laura Rodriguez de la Fuente, Andrew M K Law, Laura Rangel-Sanchez, Jeron Venhuizen, Fiona Steffan, Lesley Castillo, Robin L Anderson, Fatima Valdes-Mora, David Gallego-Ortega

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Laura Rodriguez de la FuenteFaculty of Engineering and IT, School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW, Australia.
Andrew M K LawThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Laura Rangel-SanchezFaculty of Engineering and IT, School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW, Australia.
Jeron VenhuizenThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Fiona SteffanThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Lesley CastilloThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Robin L AndersonOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
Fatima Valdes-Mora *Faculty of Engineering and IT, School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW, Australia. fvaldesmora@ccia.org.au.
David Gallego-Ortega *Faculty of Engineering and IT, School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW, Australia. David.GallegoOrtega@uts.edu.au.

Funding

Cancer Council NSW RG18-03Cancer Institute NSW CDF181218Department of Education, Australian Government RTP ScholarshipNational Breast Cancer Foundation IIRS21-068University of New South Wales UPA Scholarship
6 · The paper itself

Abstract

backgroundThis study uses the well-established 4T1.2 and 67NR mammary cancer cell lines as syngeneic immunocompetent implantable murine models of triple negative breast cancer.

methodsUsing pair-wise analysis, we compare the implantation route of cancer cells by conventional orthotopic injections in the mammary fat pad vs intraductal injection in the mammary ductal tree. We reveal that implantation methodology influences the inherent metastatic potential, tumour progression and the co-evolution of cancer cells and the tumour microenvironment.

resultsIntraductal injection accelerates tumour growth, especially in the non-metastatic 67NR model, and better mimics early tumourigenic events that preserve the tissue microenvironment crucial for tumour-stromal interactions. Immune cell composition differences are driven by the tumour model but independent of the implantation method, however, intraductal implantation carries higher stromal proportions at early stages of tumour development. In the 4T1.2 model, intraductal injection increases metastatic burden. We found markedly different systemic inflammation traits unique to the metastatic 4T1.2 scenario consistent with the acquisition of a cancer immunotolerant phenotype during progression to metastatic disease. Metastatic dissemination induced a myeloid-dominated inflammatory milieu, particularly driven by granulocytic myeloid-derived suppressor cells, contrasting with the lymphocyte-rich profile in the non-metastatic 67NR tumours. Immune responses of the metastatic 4T1.2 scenario were further analysed by targeted single-cell RNA sequencing revealing distinct immune activation in primary tumours, emphasising the differential role of immune cells between primary and metastatic lesions.

conclusionsOur findings stress the importance of carefully selecting experimental models to faithfully recapitulate breast cancer progression and metastasis, providing insights for future therapeutic interventions focused on immune modulation.

Indexed as

Triple Negative Breast NeoplasmsTumor MicroenvironmentAnimalsCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleHumansMiceMyeloid-Derived Suppressor CellsNeoplasm Metastasis4T1.2Lung metastasisMINDMyeloid-derived suppressor cellsPre-clinical mouse modelsTriple negative breast cancerTumour and metastatic immune microenvironment

Identifiers

PMID41372751
PMCPMC12802248

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LicenceCC BY-NC-ND
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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.