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

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

  • Cancer Cell. 2024 Jul 11:S1535-6108(24)00239-3. doi: 10.1016/j.ccell.2024.06.014.
Siyuan You 1,  Shuqin Li 1,  Lingsu Zeng 2,  Jinsheng Song 1,  Zifeng Li 1,  Weiyun Li 1,  Hengxiao Ni 1,  Xu Xiao 3,  Wenbo Deng 4,  Hongye Li 1,  Wenbo Lin 1,  Chenyu Liang 1,  Yanfei Zheng 1,  Shih-Chin Cheng 5,  Nengming Xiao 1,  Mengsha Tong 6,  Rongshan Yu 3,  Jialiang Huang 1,  Hongling Huang 1,  Hongzhi Xu 7,  Jiahuai Han 1,  Jianlin Ren 7,  Kairui Mao 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University; Xiamen, Fujian 361102, China.
  • 2 Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China; Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province, Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Xiamen, Fujian 361004, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350001, China.
  • 3 School of Informatics, Xiamen University, Xiamen, Fujian 361005, China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian 361005, China.
  • 4 Key Laboratory of Reproductive Health Research, Fujian Province University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • 5 State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University; Xiamen, Fujian 361102, China; Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • 6 State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University; Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian 361005, China.
  • 7 Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China; Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province, Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Xiamen, Fujian 361004, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • 8 State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University; Xiamen, Fujian 361102, China; Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: maok@xmu.edu.cn.
PMID: 39029466 DOI: 10.1016/j.ccell.2024.06.014
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.

Keywords

antigen trafficking; lymphatics; mregDC; multiplex imaging; regulatory T cells; tumor microenvironment.

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