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

IF 4.7 3区 医学 Q2 IMMUNOLOGY
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
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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.

TLR9在乳腺癌中的下调:在肿瘤免疫、炎症反应和细胞衰老中的作用
toll样受体9 (TLR9)主要在人树突状细胞和B细胞中表达,并识别来自病原体的双链DNA基序来启动炎症反应。最近的研究揭示了TLR9在免疫反应中的作用,特别是在各种癌症如头颈癌、宫颈癌和卵巢癌的肿瘤发生过程中。在这项研究中,免疫组织化学(IHC)分析显示,与正常乳腺组织上皮相比,乳腺癌肿瘤中的TLR9水平显著降低。与未转化的乳腺上皮细胞系相比,在几种转化的乳腺癌细胞系中也观察到这种下调。此外,表达外源性TLR9的MDA-MB-361乳腺癌细胞表现出集落生长减少和衰老标志物IL-6、促炎细胞因子CCL2、CXCL1趋化因子的增加;和生长因子GM-CSF。这些发现支持了TLR9在缓解乳腺癌中的调节作用,并强调了其在先天免疫和肿瘤细胞生长之间的重要联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
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.
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