Zhao et al. showed that mice with late-stage tumors exhibited reduced viral antigen-specific CD8+ T cell response and had deficient protection against viral infection. Surprisingly, increased levels of CD45+CD71+TER119+ erythroid progenitor cells (EPCs) were found in the spleen, correlating with tumor burden and anemia. EPCs outnumbered MDSCs and Tregs in the spleen. Mechanistically, EPCs exerted immunosuppressive effects on T cells via increased production of reactive oxygen species (ROS) at levels similar to those produced by MDSCs. Similar results were observed in the peripheral blood of cancer patients with moderate to severe anemia.
Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection(1-3). This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia(2), 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.
Author Info: (1) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (2) Department of Immunology, School of Basic Medicine, Tongji Medical College, Huaz
Author Info: (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 Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (4) Institute of Immunology, Third Military Medical University, Chongqing, China. (5) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (6) Department of Immunology, Duke University Medical Center, Durham, NC, USA. (7) Department of Immunology, Duke University Medical Center, Durham, NC, USA. (8) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (9) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (10) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (11) Institute of Immunology, Third Military Medical University, Chongqing, China. (12) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (13) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (14) 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. (15) Institute of Immunology, Third Military Medical University, Chongqing, China. (16) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (17) Institute of Immunology, Third Military Medical University, Chongqing, China. (18) College of Pharmacy, Third Military Medical University, Chongqing, China. (19) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (20) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. (21) Department of Immunology, Duke University Medical Center, Durham, NC, USA. (22) Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, University of London, London, UK. (23) 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. (24) Departement of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. (25) Department of Immunology, Duke University Medical Center, Durham, NC, USA. qi-jing.li@duke.edu. (26) Institute of Immunology, Third Military Medical University, Chongqing, China. yelilinlcmv@163.com. (27) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. b.davis.zhu@gmail.com. Chongqing Key Laboratory of Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing, China. b.davis.zhu@gmail.com.
