Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells

IF 2.9 4区 医学 Q2 CELL BIOLOGY
Konkonika Roy , Tomasz Jędrzejewski , Justyna Sobocińska , Paulina Spisz , Bartosz Maciejewski , Nadine Hövelmeyer , Benedetta Passeri , Sylwia Wrotek
{"title":"Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells","authors":"Konkonika Roy ,&nbsp;Tomasz Jędrzejewski ,&nbsp;Justyna Sobocińska ,&nbsp;Paulina Spisz ,&nbsp;Bartosz Maciejewski ,&nbsp;Nadine Hövelmeyer ,&nbsp;Benedetta Passeri ,&nbsp;Sylwia Wrotek","doi":"10.1016/j.cellimm.2025.104934","DOIUrl":null,"url":null,"abstract":"<div><div>Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LPS, they produce inflammatory mediators that drive the primary immune response. However, this response is significantly diminished during the establishment of ET, creating an immunosuppressive environment. This environment can facilitate the development and progression of malignant conditions, including cancer.</div><div>Our research focused on the interactions between immune cells and the tumor microenvironment under ET conditions. Through comprehensive <em>in vivo</em> and <em>in vitro</em> studies employing various research techniques, we have demonstrated that interactions between endotoxin-tolerant macrophages (Mo<sub>ET</sub>) and cancer cells contribute to a pro-tumorigenic condition. Notably, we observed that Mo<sub>ET</sub> adapt a pro-tumorigenic, immunosuppressive M2 phenotype (CD163 expression). These macrophages involves distinct metabolic pathways, not depending solely on glycolysis and oxidative phosphorylation. Furthermore, our <em>in vivo</em> findings revealed macrophage infiltration within tumors under both ET and non-ET conditions, highlighting the suppressed immune landscape in the presence of ET. These findings suggest that ET plays a pivotal role in shaping tumor-associated immune responses and that targeting ET pathways could offer a novel and promising therapeutic approach for cancer treatment.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104934"},"PeriodicalIF":2.9000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S000887492500019X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LPS, they produce inflammatory mediators that drive the primary immune response. However, this response is significantly diminished during the establishment of ET, creating an immunosuppressive environment. This environment can facilitate the development and progression of malignant conditions, including cancer.
Our research focused on the interactions between immune cells and the tumor microenvironment under ET conditions. Through comprehensive in vivo and in vitro studies employing various research techniques, we have demonstrated that interactions between endotoxin-tolerant macrophages (MoET) and cancer cells contribute to a pro-tumorigenic condition. Notably, we observed that MoET adapt a pro-tumorigenic, immunosuppressive M2 phenotype (CD163 expression). These macrophages involves distinct metabolic pathways, not depending solely on glycolysis and oxidative phosphorylation. Furthermore, our in vivo findings revealed macrophage infiltration within tumors under both ET and non-ET conditions, highlighting the suppressed immune landscape in the presence of ET. These findings suggest that ET plays a pivotal role in shaping tumor-associated immune responses and that targeting ET pathways could offer a novel and promising therapeutic approach for cancer treatment.
内毒素引物和内毒素耐受性对巨噬细胞对癌细胞反应的不同影响
内毒素耐受(ET)是免疫细胞(如巨噬细胞)反复暴露于内毒素(如脂多糖(LPS))时产生的一种适应性现象。最初,当巨噬细胞被LPS激活时,它们产生炎症介质,驱动初级免疫反应。然而,这种反应在ET建立期间显著减弱,形成免疫抑制环境。这种环境可以促进恶性疾病的发展和进展,包括癌症。我们的研究重点是在ET条件下免疫细胞与肿瘤微环境的相互作用。通过采用各种研究技术的综合体内和体外研究,我们已经证明内毒素耐受巨噬细胞(MoET)和癌细胞之间的相互作用有助于促肿瘤发生。值得注意的是,我们观察到MoET具有促肿瘤、免疫抑制的M2表型(CD163表达)。这些巨噬细胞涉及不同的代谢途径,而不仅仅依赖于糖酵解和氧化磷酸化。此外,我们的体内研究结果显示,在ET和非ET条件下,肿瘤内的巨噬细胞浸润,突出了ET存在下的免疫抑制景观。这些研究结果表明,ET在形成肿瘤相关免疫反应中起着关键作用,靶向ET途径可能为癌症治疗提供一种新颖而有前途的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信