Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity

IF 48.8 1区 医学 Q1 CELL BIOLOGY
{"title":"Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity","authors":"","doi":"10.1016/j.ccell.2024.06.014","DOIUrl":null,"url":null,"abstract":"<p>The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":48.8000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2024.06.014","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.

Abstract Image

淋巴定位的Treg-mregDC串扰限制了抗原贩运并抑制了抗肿瘤免疫力
肿瘤微环境(TME)对肿瘤生长和免疫疗法的疗效有重大影响。然而,肿瘤微环境中驱动这些影响的精确细胞相互作用和空间组织仍然难以捉摸。利用先进的多重成像技术,我们发现调节性 T 细胞(Tregs)聚集在外周肿瘤基质的淋巴管周围。富含免疫调节分子的成熟树突状细胞(mregDCs)促进了这种局部聚集,从而促进了Tregs的趋化,建立了一个淋巴管周围Treg-mregDC生态位。在这个生态位内,mregDCs 促进 Treg 的活化,进而抑制肿瘤抗原向引流的肠系膜淋巴结的迁移,从而阻碍抗肿瘤适应性免疫反应的启动。破坏 Treg 对 mregDCs 的招募可抑制肿瘤进展。我们的研究为了解TME的组织以及淋巴细胞和髓系细胞之间的局部串扰如何抑制抗肿瘤免疫反应提供了宝贵的见解。
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
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
×
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:481959085
Book学术官方微信