Evidence map›Paper›PMID 26243145›Full record

ArticleBreast cancer research : BCR2015

Human breast cancer cells educate macrophages toward the M2 activation status.

Sofia Sousa, Régis Brion, Minnamaija Lintunen, Pauliina Kronqvist, Jouko Sandholm, Jukka Mönkkönen, Pirkko-Liisa Kellokumpu-Lehtinen, Susanna Lauttia, Olli Tynninen, Heikki Joensuu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
252citing papers in PubMed, 1 pooled it
10.9field-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

252 citing papers in PubMed, 1 synthesis or guideline pooled it, 420 citations in OpenAlex.

  1. Pooled it
  2. Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026
    Article
  3. Article
  4. Review
  5. Autophagy · 2026
    Article
  6. Article
  7. Article
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  17. Article
  18. Genes · 2025
    Article
  19. Review
  20. Roles of Peripheral Nerves in Tumor Initiation and Progression.International journal of molecular sciences · 2025
    Review

192 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

12 authors at 7 institutions in 2 countries.

Sofia SousaSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, P.O. Box 1627, FI-70211, Kuopio, Finland. sofia.sousa@uef.fi.
Régis BrionINSERM, UMR957, Equipe LIGUE 2012, Nantes, F-44035, France. regis.brion@univ-nantes.fr.
Minnamaija LintunenInstitute of Biomedicine, Department of Cell Biology and Anatomy, University of Turku, Turku, Finland. minnamaija.lintunen@utu.fi.
Pauliina KronqvistInstitute of Biomedicine, Department of Cell Biology and Anatomy, University of Turku, Turku, Finland. paukro@utu.fi.
Jouko SandholmCell Imaging Core, Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland. jouko.sandholm@btk.fi.
Jukka MönkkönenSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, P.O. Box 1627, FI-70211, Kuopio, Finland. jukka.monkkonen@uef.fi.
Pirkko-Liisa Kellokumpu-LehtinenMedical School, University of Tampere and Department of Oncology Tampere University Hospital, Tampere, Finland. pirkko-liisa.kellokumpu-lehtinen@uta.fi.
Susanna LauttiaLaboratory of Molecular Oncology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. susanna.lauttia@helsinki.fi.
Olli TynninenDepartment of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland. olli.tynninen@hus.fi.
Heikki JoensuuLaboratory of Molecular Oncology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. heikki.joensuu@hus.fi.
Dominique HeymannINSERM, UMR957, Equipe LIGUE 2012, Nantes, F-44035, France. dominique.heymann@univ-nantes.fr.
Jorma A MäättäSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, P.O. Box 1627, FI-70211, Kuopio, Finland. jorma.maatta@utu.fi.
University of Helsinki · FIUniversity of Turku · FIUniversity of Eastern Finland · FIÅbo Akademi University · FICentre Hospitalier Universitaire de Nantes · FRInserm · FRTampere University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumor type. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2-macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. The role of TAMs is not fully understood in breast cancer progression.

methodsMacrophage infiltration (CD68) and activation status (HLA-DRIIα, CD163) were evaluated in a large cohort of human primary breast tumors (562 tissue microarray samples), by immunohistochemistry and scored by automated image analysis algorithms. Survival between groups was compared using the Kaplan-Meier life-table method and a Cox multivariate proportional hazards model. Macrophage education by breast cancer cells was assessed by ex vivo differentiation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of breast cancer cell conditioned media (MDA-MB231, MCF-7 or T47D cell lines) and M1 or M2 inducing cytokines (respectively IFN-γ, IL-4 and IL-10). Obtained macrophages were analyzed by flow cytometry (CD14, CD16, CD64, CD86, CD200R and CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) and zymography (matrix metalloproteinase 9, MMP-9).

resultsClinically, we found that high numbers of CD163(+) M2-macrophages were strongly associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological ductal type (p<0.001) in the studied cohort of human primary breast tumors. We demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype. Furthermore, the more aggressive mesenchymal-like cell line MDA-MB231, which secretes high levels of M-CSF, skews macrophages toward the more immunosuppressive M2c subtype.

conclusionsThis study demonstrates that human breast cancer cells influence macrophage differentiation and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.

Indexed as

Breast NeoplasmsCell DifferentiationCell Line, TumorCell ProliferationCytokinesFemaleHumansLeukocytes, MononuclearMacrophage Colony-Stimulating FactorMacrophagesMatrix Metalloproteinase 9CytokinesMacrophage Colony-Stimulating FactorMatrix Metalloproteinase 9

Identifiers

PMID26243145
PMCPMC4531540
OpenAlexW1919137762

What OpenQuestion holds

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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 OpenQuestion graph.