Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis

doi:10.1172/JCI97973

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	Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis
	Chen, Min-Shan 1; Wu, Chong 1,2; Ning, Huiheng 2; Liu, Mingyu 2; Lin, Jie 2; Luo, Shufeng 2; Zhu, Wenjie 1; Xu, Jing 1; Wu, Wen-Chao 1; Liang, Jing 3
刊名	JOURNAL OF CLINICAL INVESTIGATION
	2018-08-01
卷号	128 期号:8 页码:3425-3438
ISSN号	0021-9738
DOI	10.1172/JCI97973
英文摘要	Cancer progression is associated with alterations of intra-and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here, we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs). With the distinct capability to produce and respond to granulocyte-macrophage CSF (GM-CSF), these splenic HSPCs were "primed" and committed to generating immunosuppressive myeloid cells. Mechanistically, the CCL2/CCR2 axis-dependent recruitment and the subsequent local education by the splenic stroma were critical for eliciting this splenic HSPC response. Selective abrogation of this splenic EMH was sufficient to synergistically enhance the therapeutic efficacy of immune checkpoint blockade. Clinically, patients with different types of solid tumors exhibited increased splenic HSPC levels associated with poor survival. These findings reveal a unique and important role of splenic hematopoiesis in tumor-associated myelopoiesis.
资助项目	National Key R&D Program of China[2017YFA0505803] ; National Key R&D Program of China[2018ZX10302205] ; National Natural Science Foundation of China[91442205] ; National Natural Science Foundation of China[81730044] ; Health Medical Collaborative Innovation Program of Guangzhou[201400000001-3] ; Fundamental Research Funds for the Central Universities[16lgjc46] ; Fundamental Research Funds for the Central Universities[171gjc32]
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	AMER SOC CLINICAL INVESTIGATION INC
WOS记录号	WOS:000440461500026
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/5575]
专题	中国科学院武汉植物园
通讯作者	Zheng, Limin
作者单位	1.Sun Yat Sen Univ, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Ctr Canc, Guangzhou, Guangdong, Peoples R China 2.Sun Yat Sen Univ, Key Lab Gene Engn, Minist Educ, Guangzhou, Guangdong, Peoples R China 3.Sun Yat Sen Univ, Dept Pathol, Guangdong Key Lab Liver Dis Res, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China 4.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Chen, Min-Shan,Wu, Chong,Ning, Huiheng,et al. Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis[J]. JOURNAL OF CLINICAL INVESTIGATION,2018,128(8):3425-3438.
APA	Chen, Min-Shan.,Wu, Chong.,Ning, Huiheng.,Liu, Mingyu.,Lin, Jie.,...&Zheng, Limin.(2018).Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis.JOURNAL OF CLINICAL INVESTIGATION,128(8),3425-3438.
MLA	Chen, Min-Shan,et al."Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis".JOURNAL OF CLINICAL INVESTIGATION 128.8(2018):3425-3438.