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

IF 48.8 1区 医学 Q1 CELL BIOLOGY Cancer Cell Pub Date : 2024-07-18 DOI:10.1016/j.ccell.2024.06.014
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引用次数: 0

摘要

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

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.

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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.
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