title: IRF7 regulates the development of granulocytic myeloid-derived suppressor cells through S100A9 transrepression in cancer.
abstract: Accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles against achieving appropriate anti-tumor immune responses and successful tumor immunotherapy. Granulocytic MDSCs (G-MDSCs) are common in tumor-bearing hosts. However, the mechanisms regulating the development of MDSCs, especially G-MDSCs, remain poorly understood. In this report, we showed that interferon regulatory factor 7 (IRF7) plays an important role in the development of G-MDSCs, but not monocytic MDSCs. IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice. IRF7 deletion did not affect the suppressive activity of G-MDSCs. Mechanistic studies showed that S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein. S100A9 knockdown almost completely abrogated the effects of IRF7 deletion on G-MDSC development and tumor metastasis. Importantly, IRF7 expression levels negatively correlated with the G-MDSC frequency and tumor metastasis, as well as S100A9 expression, in cancer patients. In summary, our study demonstrated that IRF7 represents a novel regulator of G-MDSC development in cancer, which may have predictive value for tumor progression.
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Guangzhou, China.|Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|School of Basic Sciences, Guangzhou Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Guangzhou, China.|Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|School of Basic Sciences, Guangzhou Medical University, Guangzhou, China.|Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007167:Immunotherapy; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000502:physiology*; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D019139:Tumor Escape / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B; D050839:Interferon Regulatory Factor-7