2. Academic Validation
  3. Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells

Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells

  • Nat Med. 2018 Oct;24(10):1536-1544. doi: 10.1038/s41591-018-0205-5.
Lintao Zhao # 1,  Ran He # 2,  Haixia Long # 1,  Bo Guo # 3,  Qingzhu Jia 1,  Diyuan Qin 4,  Si-Qi Liu 4,  Zhongyu Wang 1,  Tong Xiang 1,  Jue Zhang 1,  Yulong Tan 3,  Jiani Huang 1,  Junying Chen 1,  Fang Wang 5,  Minglu Xiao 3,  Jianbao Gao 1,  Xinxin Yang 3,  Hao Zeng 6,  Xinxin Wang 1,  Chunyan Hu 1,  Peter B Alexander 4,  Alistair L J Symonds 7,  Jia Yu 5,  Yisong Wan 8 9,  Qi-Jing Li 10,  Lilin Ye 11,  Bo Zhu 12 13
Affiliations

Affiliations

  • 1 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
  • 2 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Institute of Immunology, Third Military Medical University, Chongqing, China.
  • 4 Department of Immunology, Duke University Medical Center, Durham, NC, USA.
  • 5 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
  • 6 College of Pharmacy, Third Military Medical University, Chongqing, China.
  • 7 Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, University of London, London, UK.
  • 8 Departement of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 9 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 10 Department of Immunology, Duke University Medical Center, Durham, NC, USA. qi-jing.li@duke.edu.
  • 11 Institute of Immunology, Third Military Medical University, Chongqing, China. yelilinlcmv@163.com.
  • 12 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. b.davis.zhu@gmail.com.
  • 13 Chongqing Key Laboratory of Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing, China. b.davis.zhu@gmail.com.
  • # Contributed equally.
PMID: 30297899 DOI: 10.1038/s41591-018-0205-5
Abstract

Impaired immunity in patients with late-stage Cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to Infection1-3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, Reactive Oxygen Species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in patients with Cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced Cancer.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z