Gr-1+CD115+ Immature Myeloid Suppressor Cells Mediate the Development of Tumor-Induced T Regulatory Cells and T-Cell Anergy in Tumor-Bearing Host
2006; American Association for Cancer Research; Volume: 66; Issue: 2 Linguagem: Inglês
10.1158/0008-5472.can-05-1299
ISSN1538-7445
AutoresBo Huang, Ping‐Ying Pan, Qingsheng Li, Alice I. Sato, David E. Levy, Jonathan S. Bromberg, Celia M. Divino, Shu‐Hsia Chen,
Tópico(s)Immune Cell Function and Interaction
ResumoAbstract The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1+CD115+ MSCs, in addition to being able to suppress T-cell proliferation in vitro, can induce the development of Foxp3+ T regulatory cells (Treg) in vivo, which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-β by Gr-1+CD115+ MSCs was induced and enhanced, respectively, on IFN-γ stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-γ and IL-10, and is independent of the nitric oxide–mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1+CD115+ MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses. (Cancer Res 2006; 66(2): 1123-31)
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