An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure

Liu, Wei1,2; You, Wenhua3,4; Lan, Zhenwei5; Ren, Yijiu6; Gao, Shuangshu7; Li, Shuchao8; Chen, Wei -Wei1; Huang, Chunyu2,9; Zeng, Yong2,9; Xiao, Nengming5; Wang, Zeshuai1; Xie, Huikang1,10; Ma, Huan1,11; Chen, Yun3; Wang, Guangsuo1,2,12; Chen, Chang6; Li, Hanjie1

2024-03-19

10.1016/j.xcrm.2024.101448

CELL REPORTS MEDICINE   影响因子和分区

2666-3791

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single -cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8 + T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4 + T cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4 + T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. Inhibiting TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The antitumoral effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL -21) -IL -21 receptor signaling. Our study establishes an anti -tumoral role of the Tfh-dependent TLS in the development of LUAD.

lymphoid structure (TLS) human lung adenocarcinoma (LUAD) outcomes. Further functional studies

SCI

英语

通讯

National Key R&D Program of China[2019YFA0906100] ; National Natural Science Foundation of China["82071767","82230059","32170919"] ; Shenzhen Science and Technology Program[KQTD20210811090115019] ; Shenzhen Institute of Synthetic Biology Scientific Research Program[JCHZ20210003] ; Jiangsu Provincial Key Research Development Program of China[BE2022770]

Cell Biology ; Research & Experimental Medicine

Cell Biology ; Medicine, Research & Experimental

WOS:001222321400001

CELL PRESS

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Key Lab Quantitat Synthet Biol, Shenzhen 518055, Peoples R China
2.Shenzhen Zhongshan Obstet & Gynecol Hosp, Shenzhen Zhongshan Inst Reprod Med & Genet, Shenzhen Key Lab Reprod Immunol Periimplantat, Shenzhen, Peoples R China
3.Wuxi Med Ctr, Collaborat Innovat Ctr Canc Personalized Med, Sch Basic Med Sci, Dept Immunol,Jiangsu Key Lab Canc Biomarkers Preve, Nanjing 211166, Jiangsu, Peoples R China
4.Southeast Univ, Sch Chem & Chem Engn, Nanjing, Peoples R China
5.Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China
6.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai, Peoples R China
7.Harbin Med Univ, Dept Pathol, Harbin, Peoples R China
8.Xiamen Univ, Dept Automat, Xiamen, Fujian, Peoples R China
9.Guangdong Engn Technol Res Ctr Reprod Immunol Peri, Shenzhen, Guangdong, Peoples R China
10.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pathol, Shanghai, Peoples R China
11.Chinese Univ Hong Kong, Sch Med Life & Hlth Sci, Shenzhen, Peoples R China
12.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Shenzhen Inst Resp Dis,Clin Med, Shenzhen, Peoples R China

Liu, Wei,You, Wenhua,Lan, Zhenwei,et al. An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure[J]. CELL REPORTS MEDICINE,2024,5(3).

Liu, Wei.,You, Wenhua.,Lan, Zhenwei.,Ren, Yijiu.,Gao, Shuangshu.,...&Li, Hanjie.(2024).An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure.CELL REPORTS MEDICINE,5(3).

Liu, Wei,et al."An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure".CELL REPORTS MEDICINE 5.3(2024).