Intratumoral CD45+CD71+ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma

• Published in: Cancer letters 2021-02, Vol.499, p.85-98
• Main Authors: Chen, Jie, Qiao, Yi-Dan, Li, Xing, Xu, Jian-Liang, Ye, Qing-Jian, Jiang, Nan, Zhang, Hui, Wu, Xiang-Yuan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies; Antigens; Antigens, CD - metabolism; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - therapy; Carcinoma, Hepatocellular - virology; CD45 antigen; Cell adhesion; Cell growth; Cells, Cultured; Coculture Techniques; Disease-Free Survival; Erythroid cells; Erythroid Cells - immunology; Erythroid Cells - metabolism; Erythropoiesis; Female; Flow cytometry; Follow-Up Studies; Hematopoiesis, Extramedullary - immunology; Hepatectomy; Hepatitis B; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - pathology; Hepatitis B, Chronic - virology; Hepatocellular carcinoma; Humans; Immune tolerance; Immunofluorescence; Immunological tolerance; Infections; Interleukin 10; Investigations; Italy - epidemiology; Kaplan-Meier Estimate; Leukocyte Common Antigens - metabolism; Liver - immunology; Liver - pathology; Liver - surgery; Liver - virology; Liver cancer; Liver Neoplasms - immunology; Liver Neoplasms - mortality; Liver Neoplasms - virology; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Middle Aged; Neonates; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - pathology; Paracrine signalling; Primary Cell Culture; Prognosis; Reactive oxygen species; Receptors, Transferrin - metabolism; Retrospective Studies; Risk Assessment - methods; Spleen; Suppressor cells; T cell receptors; T-Lymphocytes - immunology; Tumor Escape; Tumor Microenvironment - immunology; Young Adult
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2020.12.003

CD45+CD71+ erythroid cells generated through splenic extramedullary erythropoiesis have recently been found to suppress anti-infection and tumor immunity in neonates and adults with malignances. However, their role in tumor microenvironment has not been investigated. In the present study, we found that the number of CD45+CD71+ erythroid cells was significantly elevated in hepatocellular carcinoma (HCC) tissues compared to that in paratumor region and circulation. Additionally, they were more abundant in HCC tissues compared to some immune suppressive cells as well as CD45−CD71+ erythroid cells. CD45+CD71+ erythroid cells suppressed T cells through generation of reactive oxygen species, IL-10, and TGF-β in a paracrine and cell-cell contact manner, and their suppressive effect was stronger than that of myeloid-derived suppressor cells. The abundance of CD45+CD71+ erythroid cells in tumor tissue, as illustrated via immunofluorescence, predicted disease-free survival and overall survival, and its prognostic value was better than that of Cancer of the Liver Italian Program score. This study demonstrated that accumulation of intratumoral CD45+CD71+ erythroid cells in HCC tissues could play a superior immunosuppressive role in tumor microenvironment and may serve as a valuable biomarker to predict recurrence of HCC. •CD45+CD71+ erythroid cells were enriched in Chronic Hepatitis B (CHB) and hepatocellular carcinoma (HCC) tissues.•These cells suppressed T cells (both CD4+ and CD8+) by generation of ROS, IL-10, and TGF-β.•The abundance of these cells in tumor tissue predicted tumor recurrence of HCC.