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Nat Med. 2018 Oct;24(10):1536-1544. doi: 10.1038/s41591-018-0205-5. Epub 2018 Oct 8.

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

Author information

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.

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.

PMID:
30297899
PMCID:
PMC6211844
DOI:
10.1038/s41591-018-0205-5
[Indexed for MEDLINE]
Free PMC Article

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