Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced t regulatory cells and T-cell anergy in tumor-bearing host

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(+...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-01, Vol.66 (2), p.1123-1131
Main Authors: BO HUANG, PAN, Ping-Ying, QINGSHENG LI, SATO, Alice I, LEVY, David E, BROMBERG, Jonathan, DIVINO, Celia M, CHEN, Shu-Hsia
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Cell Proliferation
Clonal Anergy - immunology
Colonic Neoplasms - immunology
Cytokines - biosynthesis
Cytokines - immunology
Female
Immunosuppression
Immunotherapy
Lymphocyte Activation
Male
Medical sciences
Mice
Mice, Inbred BALB C
Pharmacology. Drug treatments
Receptor, Macrophage Colony-Stimulating Factor
Receptors, Chemokine
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes - immunology
T-Lymphocytes, Regulatory
Transfection
Tumor Cells, Cultured
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Summary: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-beta by Gr-1(+)CD115(+) MSCs was induced and enhanced, respectively, on IFN-gamma stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-gamma 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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-1299