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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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).
The authors declare no competing interests.
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Zhao, L., He, R., Long, H. et al. Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells. Nat Med 24, 1536–1544 (2018). https://doi.org/10.1038/s41591-018-0205-5
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