淋巴定位的 Treg-mregDC 串扰限制抗原运输并抑制抗肿瘤免疫。
Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity.
发表日期：2024 Aug 12
作者：
Siyuan You, Shuqin Li, Lingsu Zeng, Jinsheng Song, Zifeng Li, Weiyun Li, Hengxiao Ni, Xu Xiao, Wenbo Deng, Hongye Li, Wenbo Lin, Chenyu Liang, Yanfei Zheng, Shih-Chin Cheng, Nengming Xiao, Mengsha Tong, Rongshan Yu, Jialiang Huang, Hongling Huang, Hongzhi Xu, Jiahuai Han, Jianlin Ren, Kairui Mao
来源：
CANCER CELL
摘要：
肿瘤微环境（TME）对肿瘤生长和免疫治疗效果具有重大影响。然而，TME 内驱动这些效应的精确细胞相互作用和空间组织仍然难以捉摸。使用先进的多重成像技术，我们发现调节性 T 细胞 (Treg) 在外周肿瘤基质的淋巴管周围聚集。这种局部积累是由富含免疫调节分子 (mregDC) 的成熟树突细胞促进的，这些细胞促进 Tregs 的趋化性，建立淋巴周围 Treg-mregDC 生态位。在这个生态位中，mregDC 促进 Treg 激活，进而抑制肿瘤抗原向引流肠系膜淋巴结的运输，从而阻碍抗肿瘤适应性免疫反应的启动。破坏 Treg 向 mregDC 的募集可抑制肿瘤进展。我们的研究为 TME 的组织以及淋巴细胞和骨髓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。版权所有 © 2024 Elsevier Inc. 保留所有权利。
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.Copyright © 2024 Elsevier Inc. All rights reserved.