Published online before print February 19, 2008

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(Journal of Leukocyte Biology. 2008;83:1136-1144.)
© 2008 by Society for Leukocyte Biology

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

Naoki Umemura^*,,1, Masanao Saio^,1,2, Tatsuhiko Suwa, Yusuke Kitoh, Juncheng Bai, Kenichi Nonaka^,, Guan-Feng Ouyang, Makoto Okada^,, Margit Balazs^||, Roza Adany^||, Toshiyuki Shibata^* and Tsuyoshi Takami

^* Departments of Oral and Maxillofacial Sciences,
Immunopathology,
Surgical Oncology, and
Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan; and
^|| Department of Preventive Medicine, University of Debrecen, Hungary

²Correspondence: Gifu University Graduate School of Medicine, Dept. of Immunopathology, 2S29 School of Medicine, Main Building, 1-1 Yanagido, Gifu-city, Gifu 501-1194 Japan. E-mail: saio{at}gifu-u.ac.jp

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-4R⁺ 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- 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.

Key Words: myeloid-derived suppressor cells • TGF-β

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