Abstract
Abstract CD200, a transmembrane protein expressed on multiple cell types, regulates anti-tumor immunity in animal models. Its overexpression is associated with a poor prognosis in human AML, MM, and melanoma. Blockade of CD200 expression on CD200-expressing tumor cells using CD200-specific monoclonal antibodies or siRNA enhanced anti-tumor immunity against tumor cells both in vitro and in vivo. A soluble variant of CD200 (sCD200) is detectable in human serum, and patients with Chronic lymphocytic leukemia show elevated serum levels. We investigated the correlation between serum sCD200 levels and clinical disease in CLL patients. sCD200 levels are associated with Rai disease stage and lymphocyte-doubling time. Shedding of cell surface CD200 from CLL cells in vitro can be induced by PMA and TLR7 agonists, with patient-to-patient variability. Shedding of CD200 is correlated with patient serum sCD200 levels, suggesting that inherent differences of CLL cells in responses to shedding stimuli may have clinical significance. sCD200 levels in serum may provide prognostic and/or diagnostic information in CLL, and may contribute to the efficacy of treatments targeting cell-surface CD200.
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