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, M. Balázs, R. Ádány, Toshiyuki Shibata, Tsuyoshi Takami

Research output: Contribution to journalArticle

235 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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Monocytes
Macrophages
Neoplasms
Exudates and Transudates
Phenotype
Messenger RNA
Macrophage Activation
Myeloid-Derived Suppressor Cells
Interleukin-1
Glioma
Anti-Idiotypic Antibodies
Colon
Adenocarcinoma
Cytokines
T-Lymphocytes
Proteins

Keywords

  • Myeloid-derived suppressor cells
  • TGF-β

ASJC Scopus subject areas

  • Cell Biology

Cite this

Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. / Umemura, Naoki; Saio, Masanao; Suwa, Tatsuhiko; Kitoh, Yusuke; Bai, Juncheng; Nonaka, Kenichi; Ouyang, Guan Feng; Okada, Makoto; Balázs, M.; Ádány, R.; Shibata, Toshiyuki; Takami, Tsuyoshi.

In: Journal of Leukocyte Biology, Vol. 83, No. 5, 01.05.2008, p. 1136-1144.

Research output: Contribution to journalArticle

Umemura, Naoki ; Saio, Masanao ; Suwa, Tatsuhiko ; Kitoh, Yusuke ; Bai, Juncheng ; Nonaka, Kenichi ; Ouyang, Guan Feng ; Okada, Makoto ; Balázs, M. ; Ádány, R. ; Shibata, Toshiyuki ; Takami, Tsuyoshi. / Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. In: Journal of Leukocyte Biology. 2008 ; Vol. 83, No. 5. pp. 1136-1144.
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AU - Kitoh, Yusuke

AU - Bai, Juncheng

AU - Nonaka, Kenichi

AU - Ouyang, Guan Feng

AU - Okada, Makoto

AU - Balázs, M.

AU - Ádány, R.

AU - Shibata, Toshiyuki

AU - Takami, Tsuyoshi

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AB - 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.

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