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

. 2008 May;83(5):1136-44.

doi: 10.1189/jlb.0907611. Epub 2008 Feb 19.

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

Affiliations

• PMID: 18285406
• DOI: 10.1189/jlb.0907611

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

Naoki Umemura et al. J Leukoc Biol. 2008 May.

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.

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