Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1,2,3. 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.

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Data availability

All original data used in this study are available upon request. All published noncommercial reagents can be made available upon request. The RNA-seq data are available through GEO repository (GSE106384).

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MMTV-PyMT mice were kindly provided by X. Liu (State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai). P14 (CD90.1) TCR transgenic mice were obtained from R. Ahmed at Emory University. Q.-J.L. is a Whitehead Family Foundation Scholar and supported by the National Institute of Allergy and Infectious Disease (NIAID; R01-AI091878), the National Cancer Institute (NCI; P50-CA190991), and the National Institutes of Health (NIH) Beau Biden Cancer Moonshot Initiative (R33CA225328). This work is also supported by the National Nature Science Foundation of China (grant nos. 81472648, 81500089, 81620108023, 81222031, 81773041 and 31600733), by the Research on The Basis and Frontier of Chongqing (grant nos. cstc2016jcyjA0049).

Author information

Author notes

  1. These authors contributed equally to this work: Lintao Zhao, Ran He, Haixia Long, Bo Guo.


  1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China

    • Lintao Zhao
    • , Haixia Long
    • , Qingzhu Jia
    • , Zhongyu Wang
    • , Tong Xiang
    • , Jue Zhang
    • , Jiani Huang
    • , Junying Chen
    • , Jianbao Gao
    • , Xinxin Wang
    • , Chunyan Hu
    •  & Bo Zhu
  2. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    • Ran He
  3. Institute of Immunology, Third Military Medical University, Chongqing, China

    • Bo Guo
    • , Yulong Tan
    • , Minglu Xiao
    • , Xinxin Yang
    •  & Lilin Ye
  4. Department of Immunology, Duke University Medical Center, Durham, NC, USA

    • Diyuan Qin
    • , Si-Qi Liu
    • , Peter B. Alexander
    •  & Qi-Jing Li
  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

    • Fang Wang
    •  & Jia Yu
  6. College of Pharmacy, Third Military Medical University, Chongqing, China

    • Hao Zeng
  7. Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, University of London, London, UK

    • Alistair L. J. Symonds
  8. Departement of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Yisong Wan
  9. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Yisong Wan
  10. Chongqing Key Laboratory of Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing, China

    • Bo Zhu


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L.Z., R.H., H.L., and B.G. performed experiments, analyzed data, and drafted the manuscript with comments from all authors. Q.J. is responsible for transcriptome analysis. D.Q. and S.-Q.L. performed Lm infection and EPC depletion experiments. Z.W., T.X., J.Z., Y.T., J.H., J.C., F.W., M.X., J.G., X.Y., H.Z., X.W., and C.H. assisted or independently performed some experiments (FACS, ELISPOT assay, real-time qPCR and so on). P.B.A., A.L.J.S., J.Y., and Y.W. provided critical reagents, technical support, or clinical samples. They also provided help in writing this manuscript. L.Z. generated the initial hypothesis, and Q.-J. L. and B. Z. conceptualized this study. Q.-J. L., L.Y., and B.Z. supervised the project, designed experiments, interpreted data, and wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Qi-Jing Li or Lilin Ye or Bo Zhu.

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