A critical role of CD200R signaling in limiting the growth and metastasis of CD200 positive melanoma

CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells. However, its roles in tumor growth and immunity are n...

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Published in:The Journal of immunology (1950) 2016-07, Vol.197 (4), p.1489-1497
Main Authors: Liu, Jin-Qing, Talebian, Fatemeh, Wu, Lisha, Liu, Zhihao, Li, Ming-Song, Wu, Laichu, Zhu, Jianmin, Markowitz, Joseph, Carson, William E., Basu, Sujit, Bai, Xue-Feng
Format: Article
Language:English
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Summary:CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells. However, its roles in tumor growth and immunity are not clearly understood. In this study, we have used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200-positive, but not CD200-negative B16 tumors. Strikingly, CD200R-deficient mice receiving CD200-positive B16 cells intravenously exhibited massive tumor growth in multiple organs including liver, lung, kidney and peritoneal cavity, while the growth of the same tumors in wild type mice is limited. CD200-positive tumors grown in CD200R-deficient mice contained higher numbers of CD11b + Ly6C + myeloid cells, exhibited increased expression of VEGF and HIF-1α genes with increased angiogenesis and showed significantly reduced infiltration of CD4 + and CD8 + T cells, presumably due to reduced expression of T cell chemokines such as CXCL9 and CXCL16. The Liver from CD200R-deficient mice under metastatic growth of CD200-positive tumors contained significantly increased numbers of CD11b + Gr1 - myeloid cells, FoxP3 + regulatory T cells and reduced numbers of NK cells. Liver T cells also had reduced capacity in the production of IFN-γ or TNF-α. Taken together, we have revealed a critical role of CD200R signaling in limiting the growth and metastasis of CD200 positive tumors. Targeting CD200R signaling may thus has a potential to interfere with the metastatic growth of CD200-positive tumors like melanoma.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1600052