title: Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics.
abstract: Here, tumor-infiltrating CD11b(+) myelomonocytoid cells in murine colon adenocarcinoma-38 and GL261 murine glioma were phenotypically characterized. Over 90% were of the CD11b(+)F4/80(+) monocyte/macrophage lineage. They also had a myeloid-derived suppressor cell (MDSC) phenotype, as they suppressed the proliferation of activated splenic CD8(+) T cells and had a CD11b(+)CD11c(+)Gr-1(low)IL-4Ralpha(+) phenotype. In addition, the cells expressed CX(3)CR1 and CCR2 simultaneously, which are the markers of an inflammatory monocyte. The MDSCs expressed CD206, CXCL10, IL-1beta, and TNF-alpha mRNAs. They also simultaneously expressed CXCL10 and CD206 proteins, which are typical, classical (M1) and alternative (M2) macrophage activation markers, respectively. Peritoneal exudate cells (PECs) strongly expressed CD36, CD206, and TGF-beta mRNA, which is characteristic of deactivated monocytes. The MDSCs also secreted TGF-beta, and in vitro culture of MDSCs and PECs with anti-TGF-beta antibody recovered their ability to secrete NO. However, as a result of secretion of proinflammatory cytokines, MDSCs could not be categorized into deactivated monocyte/macrophages. Thus, tumor-infiltrating MDSCs bear pleiotropic characteristics of M1 and M2 monocytes/macrophages. Furthermore, CD206 expression by tumor-infiltrating MDSCs appears to be regulated by an autocrine mechanism that involves TGF-beta.
authors.affiliation: Department of Oral and Maxillofacial Sciences, Gifu University Graduate School of Medicine, Gifu-city, Gifu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.forename: Masanao
authors.initials: M
authors.lastname: Saio
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Suwa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kitoh
authors.forename: Juncheng
authors.initials: J
authors.lastname: Bai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Guan-Feng
authors.initials: GF
authors.lastname: Ouyang
authors.forename: Makoto
authors.initials: M
authors.lastname: Okada
authors.forename: Margit
authors.initials: M
authors.lastname: Balazs
authors.forename: Roza
authors.initials: R
authors.lastname: Adany
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D005910:Glioma / Q000276:immunology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology*
chemical_list: D049452:Green Fluorescent Proteins