B Cells and IL-21-Producing Follicular Helper T Cells Cooperate to Determine the Dynamic Alterations of Premetastatic Tumor Draining Lymph Nodes of Breast Cancer  

作　　者：Xinrui Mao Xinyu Tang Hong Pan Muxin Yu Sihan Ji Wen Qiu Nan Che Kai Zhang Zhendong Huang Yunshan Jiang Ji Wang Zhaoyun Zhong Jiaming Wang Mingduo Liu Mingkang Chen Wenbin Zhou Shui Wang 

机构地区：[1]Department of Breast Surgery,The First Affiliated Hospital with Nanjing Medical University,300 Guangzhou Road,Nanjing 210029,China [2]Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine,School of Public Health,Nanjing Medical University,Nanjing 211166,China [3]Department of Immunology,Nanjing Medical University,Nanjing 211166,China [4]Department of Rheumatology and Immunology,The First Affiliated Hospital with Nanjing Medical University,300 Guangzhou Road,Nanjing 210029,China [5]Pancreatic Center&Department of General Surgery,The First Affiliated Hospital with Nanjing Medical University,Nanjing 210029,Jiangsu,China [6]Pancreas Institute of Nanjing Medical University,Nanjing 210029,Jiangsu,China [7]Department of Pathology,The First Affiliated Hospital with Nanjing Medical University,300 Guangzhou Road,Nanjing 210029,China [8]Department of Ophthalmology,The First Affiliated Hospital with Nanjing Medical University,300 Guangzhou Road,Nanjing 210029,China

出　　处：《Research》2024年第4期562-578,共17页研究(英文)

基　　金：supported in part by the National Natural Science Foundation of China(81771953 and 82172683);a project funded by Jiangsu Provincial Science and Technology Department(BE2022807).

摘　　要：Metastasis is the major cause of cancer-related death,and lymph node is the most common site of metastasis in breast cancer.However,the alterations that happen in tumor-draining lymph nodes(TDLNs)to form a premetastatic microenvironment are largely unknown.Here,we first report the dynamic changes in size and immune status of TDLNs before metastasis in breast cancer.With the progression of tumor,the TDLN is first enlarged and immune-activated at early stage that contains specific antitumor immunity against metastasis.The TDLN is then contracted and immunosuppressed at late stage before finally getting metastasized.Mechanistically,B and follicular helper T(Tfh)cells parallelly expand and contract to determine the size of TDLN.The activation status and specific antitumor immunity of CD8+T cells in the TDLN are determined by interleukin-21(IL-21)produced by Tfh cells,thus showing parallel changes.The turn from activated enlargement to suppressed contraction is due to the spontaneous contraction of germinal centers mediated by follicular regulatory T cells.On the basis of the B-Tfh-IL-21-CD8+T cell axis,we prove that targeting the axis could activate TDLNs to resist metastasis.Together,our findings identify the dynamic alterations and regulatory mechanisms of premetastatic TDLNs of breast cancer and provide new strategies to inhibit lymph node metastasis.

关 键 词：alterations IMMUNITY METASTATIC 

分 类 号：R73[医药卫生—肿瘤]