Emily Sible, Gregory Weitsman, Salome Amouyal, Guillaume Roblot, Marie Marotel, Rémi Pescarmona, Nathalie Bendriss-Vermare, Cheryl Gillett, Amie Ceesay, Alexia Gazeu, Marie Cecile Michallet, Christophe Caux, Francois-Loic Cosset, Umaima Al Alem, Tony Ng, Uzma Ayesha Hasan
{"title":"TLR9 Downregulation in Breast Cancer: Its Role in Tumor Immunity, Inflammatory Response, and Cellular Senescence.","authors":"Emily Sible, Gregory Weitsman, Salome Amouyal, Guillaume Roblot, Marie Marotel, Rémi Pescarmona, Nathalie Bendriss-Vermare, Cheryl Gillett, Amie Ceesay, Alexia Gazeu, Marie Cecile Michallet, Christophe Caux, Francois-Loic Cosset, Umaima Al Alem, Tony Ng, Uzma Ayesha Hasan","doi":"10.1159/000545527","DOIUrl":null,"url":null,"abstract":"<p><p>Toll-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 TLR9's 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. In this study, immunohistochemistry (IHC) analysis demonstrated significantly lower TLR9 levels in breast cancer tumors 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 senescence marker IL-6, pro- inflammatory cytokine CCL2, CXCL1 chemokine; and growth factor GM-CSF. These findings support TLR9's regulatory role in mitigating breast cancer and highlight its critical connection between the innate immunity and tumor cell growth.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-20"},"PeriodicalIF":4.7000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Innate Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000545527","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Toll-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 TLR9's 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. In this study, immunohistochemistry (IHC) analysis demonstrated significantly lower TLR9 levels in breast cancer tumors 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 senescence marker IL-6, pro- inflammatory cytokine CCL2, CXCL1 chemokine; and growth factor GM-CSF. These findings support TLR9's regulatory role in mitigating breast cancer and highlight its critical connection between the innate immunity and tumor cell growth.
期刊介绍:
The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.