Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics

Naoki Umemura, Masanao Saio, Tatsuhiko Suwa, Yusuke Kitoh, Juncheng Bai, Kenichi Nonaka, Guan Feng Ouyang, Makoto Okada, Margit Balazs, Roza Adany, Toshiyuki Shibata, Tsuyoshi Takami

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242 Citations (Scopus)

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 lowIL-4Rα+ phenotype. In addition, the cells expressed CX3CR1 and CCR2 simultaneously, which are the markers of an inflammatory monocyte. The MDSCs expressed CD206, CXCL10, IL-1β, and TNF-α 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-β mRNA, which is characteristic of deactivated monocytes. The MDSCs also secreted TGF-β, and in vitro culture of MDSCs and PECs with anti-TGF-β 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-β.

Original languageEnglish
Pages (from-to)1136-1144
Number of pages9
JournalJournal of Leukocyte Biology
Volume83
Issue number5
DOIs
Publication statusPublished - May 1 2008

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Keywords

  • Myeloid-derived suppressor cells
  • TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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