Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry

doi:10.1186/s13045-022-01326-z

	Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry
	Liu, Long 8,9,10; Yu, Xingxing 8,9,10; Li, Zhifeng 8,9,10; He, Xiaohua 7; Zha, Jie 8,9,10; Lin, Zhijuan 8,9,10; Hong, Yan 8,9,10; Zheng, Huijian 8,9,10; Lai, Qian 8,9,10; Ding, Kaiyang 6
刊名	JOURNAL OF HEMATOLOGY & ONCOLOGY
	2022-08-22
卷号	15
关键词	FL TIME POD Immune signature T cells
DOI	10.1186/s13045-022-01326-z
通讯作者	Li, Zhiming(lizhm@sysucc.org.cn) ; Young, Ken H.(ken.young@duke.edu) ; Xu, Bing(xubing@xmu.edu.cn)
英文摘要	Background Patients with follicular lymphoma (FL) who experience disease progression within 24 months (POD24) have inferior outcomes. The tumor immune microenvironment (TIME) plays a crucial role in pathogenesis and progression of follicular lymphoma (FL). However, TIME evolution during progression of disease within 24 months (POD24) is elusive. Methods Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively analyze the TIME structure in 13 paired FLs at diagnosis and POD24. Results Follicles and peri-follicular regions were well dissected in structure. Peri-follicular regions represented a barrier for immune infiltration into the follicles. More FL-cells in the peri-follicular regions suffered CD8(+)T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163(-) macrophages with PD-1 ligand upregulation and decreased CD8(+)T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles. Spatial analyses demonstrated that FL-cells interacted more intimately with macrophages than with Tregs and less with cytotoxic T cells in both peri-follicular regions and follicles during POD24. In comparison, macrophages also cooperated more frequently with Tregs to simultaneously hijack FL-cells, creating an enhanced immunosuppressive environment in both peri-follicular and follicular regions during POD24. Conclusions Peri-follicular regions function as a barrier by recruiting both CD8(+)T cells and immunosuppressive cells, protecting follicular FL-cells from immune attack at diagnosis or POD24. FL-cells reside in a more immune-compromised microenvironment and evade immune cell attacks during POD24. Novel immunotherapeutic approaches harnessing LAG-3, macrophages, and Tregs will be empowered to overcome poor outcomes in patients with FL POD24.
资助项目	National Natural Science Foundation of China[82170180] ; National Natural Science Foundation of China[81800163] ; National Natural Science Foundation of China[81800196] ; National Natural Science Foundation of China[81770161] ; National Natural Science Foundation of China[81900164] ; National Natural Science Foundation of China[82100204] ; Natural Science Foundation of Fujian Province[2020J011246] ; Xiamen Municipal Bureau of Science and Technology[3502Z20209003] ; Xiamen Municipal Bureau of Science and Technology[3502Z20209008] ; Lymphoma Research Fund of the Chinese Anti-Cancer Association[CORP-117]
WOS研究方向	Oncology ; Hematology
语种	英语
出版者	BMC
WOS记录号	WOS:000843839000001
资助机构	National Natural Science Foundation of China ; Natural Science Foundation of Fujian Province ; Xiamen Municipal Bureau of Science and Technology ; Lymphoma Research Fund of the Chinese Anti-Cancer Association
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/131999]
专题	中国科学院合肥物质科学研究院
通讯作者	Li, Zhiming; Young, Ken H.; Xu, Bing
作者单位	1.Duke Univ, Canc Inst, Durham, NC USA 2.Duke Univ, Med Ctr, Dept Pathol, Hematopathol Div, Durham, NC 27710 USA 3.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Dept Lymphoma, Hangzhou 310012, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Lymphoma, Hangzhou 310012, Peoples R China 5.Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Peoples R China 6.USTC Anhui Prov Hosp, Affiliated Hosp 1, Dept Hematol, Hefei 230001, Peoples R China 7.Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Dept Med Oncol,Canc Ctr, 651 Dongfeng Rd East, Guangzhou, Peoples R China 8.Key Lab Xiamen Diag & Treatment Hematol Malignanc, Xiamen 361003, Peoples R China 9.Xiamen Univ, Inst Hematol, Sch Med, Xiamen 361003, Peoples R China 10.Xiamen Univ, Affiliated Hosp 1, Dept Hematol, Xiamen 361003, Peoples R China
推荐引用方式 GB/T 7714	Liu, Long,Yu, Xingxing,Li, Zhifeng,et al. Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry[J]. JOURNAL OF HEMATOLOGY & ONCOLOGY,2022,15.
APA	Liu, Long.,Yu, Xingxing.,Li, Zhifeng.,He, Xiaohua.,Zha, Jie.,...&Xu, Bing.(2022).Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.JOURNAL OF HEMATOLOGY & ONCOLOGY,15.
MLA	Liu, Long,et al."Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry".JOURNAL OF HEMATOLOGY & ONCOLOGY 15(2022).