Evidence map›Paper›PMID 40550227›Full record

ArticleJournal of innate immunity2025

TLR9 Downregulation in Breast Cancer: Its Role in Tumor Immunity, Inflammatory Response, and Cellular Senescence.

Emily Sible, Gregory Weitsman, Salome Amouyal, Guillaume Roblot, Marie Marotel, Rémi Pescarmona, Nathalie Bendriss-Vermare, Cheryl Gillett, Amie Ceesay, Alexia Gazeu and 6 more

Abstract read
In one paragraph

Article in Journal of innate immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

16 authors.

Emily SibleCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Gregory WeitsmanKing's College London, London, UK.
Salome AmouyalCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Guillaume RoblotCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Marie MarotelCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Rémi PescarmonaCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Nathalie Bendriss-VermareCancer Research Centre of Lyon, CRCL, INSERM U1052-CNRS UMR5286, Lyon, France.
Cheryl GillettSchool of Cancer on Pharmaceutical Sciences, King's College London, Guy's Campus, London, UK.
Amie CeesayCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Alexia GazeuDivision of Cancer Studies, Research Oncology, Guy's Hospital, King's College London, London, UK.
Marie Cecile MichalletDivision of Cancer Studies, Research Oncology, Guy's Hospital, King's College London, London, UK.
Christophe CauxDivision of Cancer Studies, Research Oncology, Guy's Hospital, King's College London, London, UK.
Francois-Loic CossetCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.
Umaima Al AlemDivision of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois, USA.
Tony NgKing's College London, London, UK.
Uzma Ayesha HasanCentre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionToll-like receptor 9 (TLR9) is primarily expressed in human dendritic and B cells and recognizes double-stranded DNA motifs from pathogens to initiate an inflammatory response. Recent studies have revealed TLR9s' involvement beyond its conventional role in the immune response, notably during the tumorigenesis of various cancers such as head and neck, cervical, and ovarian cancers.

methodsIn this study patient biopsies of breast cancer tumors and normal breast epithelium were analyzed by immunohistochemistry to examine TLR9 expression. The study also investigated downregulation in transformed breast cancer cell lines compared to untransformed breast epithelial cells by analyzing gene or protein expression, including TLR9, IL-6, CCL2, CXCL1, and GM-CSF. MDA-MB-361 cells were engineered to express exogenous TLR9, and the effects on colony growth and senescence were assessed using colony formation assays, senescence staining, cytokine analysis, and flow cytometry.

resultsTLR9 levels in breast cancer tumors were significantly reduced compared to normal breast tissue epithelium. This downregulation was also observed in several transformed breast cancer cell lines compared to untransformed breast epithelial cell lines. Furthermore, MDA-MB-361 breast cancer cells expressing exogenous TLR9 exhibited reduced colony growth and an increase in the senescence marker IL-6, pro-inflammatory cytokine CCL2, CXCL1 chemokine; and growth factor GM-CSF.

conclusionThese findings support TLR9's regulatory role in mitigating breast cancer and highlight its critical connection between the innate immunity and tumor cell growth.

Indexed as

Breast NeoplasmsInflammationToll-Like Receptor 9Cell Line, TumorCellular SenescenceChemokine CCL2Chemokine CXCL1Down-RegulationEpithelial CellsFemaleGene Expression Regulation, NeoplasticGranulocyte-Macrophage Colony-Stimulating FactorHumansInterleukin-6Chemokine CCL2Chemokine CXCL1Granulocyte-Macrophage Colony-Stimulating FactorInterleukin-6TLR9 protein, humanToll-Like Receptor 9Breast cancerCell cycleSenescenceTLR9

Identifiers

PMID40550227
PMCPMC12310192

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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.