Breast cancer cell CD200 expression regulates immune response to EMT6 tumor cells in mice
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CD200 has been characterized as an important immunoregulatory molecule, increased expression of which can lead to decreased transplant rejection, autoimmunity, and allergic disease. Elevated CD200 expression has been reported to be associated with poor prognosis in a number of human malignancies. We have found that cells of the transplantable EMT6 mouse breast cancer line growing in vitro express low levels of CD200, but levels increase markedly during growth in immunocompetent mice. Similar increased in vivo expression does not occur in NOD-SCID.IL-2γr−/− mice or mice with generalized over-expression of a CD200 transgene. In both mice, tumor growth occurs faster. Altered CD200 expression in control versus transgenic mice is accompanied by reproducible changes in tumor-infiltrating host cells, and altered cell composition in lymph nodes draining the tumor (DLN). Neutralization of expressed CD200 by anti-CD200mAbs leads to decreased tumor growth in immunocompetent mice, with improved detection of cytotoxic anti-tumor immune cells in DLN. Finally, we report that tumor growth in vivo can be monitored by levels of soluble CD200 (sCD200) in serum of tumor-bearing animals.
KeywordsBreast cancer Treg CD200 transgene Immunotherapy
This study was supported by a POP II grant from the Canadian Institutes of Health Research (CIHR) to RMG.
- 12.Kretz-Rommel A, Qin FH, Dakappagari N, Ravey EP, McWhirter J, Oltean D, Frederickson S, Maruyama T, Wild MA, Nolan MJ, Wu DY, Springhorn J, Bowdish KS (2007) CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy. J Immunol 178:5595–5605PubMedGoogle Scholar
- 19.Wong K, Spaner DE, Gorczynski RM (2008) Lymphoma cell surface expression of CD200 modulates anti-tumor immunity (abstract). AAI, San DiegoGoogle Scholar
- 25.Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, Kudo S, Ochiai A (2008) Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer 113:1387–1395CrossRefPubMedGoogle Scholar
- 26.Gorczynski RM (2005) CD200 and its receptors as targets for immunoregulation. Curr Opin Invest Drugs 6:483–488Google Scholar
- 38.Cipriani B, Fridman A, Bendtsen C, Dharmapuri S, Mennuni C, Pak I, Mesiti G, Forni G, Monaci P, Bagchi A, Ciliberto G, LaMonica N, Scarselli E (2008) Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy. Hum Gene Ther 19:670–680CrossRefPubMedGoogle Scholar
- 39.Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59CrossRefPubMedGoogle Scholar