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Lymphoma cell surface expression of CD200 modulates anti‐tumor immunity
Author(s) -
Wong Karrie Ka Wai,
Gorczynski Reg,
Spaner David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.19
Subject(s) - ctl* , immunology , tumor necrosis factor alpha , cancer research , biology , antigen , tumor progression , cancer , medicine , cd8
CD200 is a transmembrane protein broadly expressed on a variety of cell types and delivers immunoregulatory signals through binding to receptor (CD200Rs) expressed on monocyte/myeloid cells and T lymphocytes. We showed in earlier reports that infusion of a soluble form of CD200, CD200Fc, into EL4 thymoma‐bearing C57/B6 mice enhanced tumor progression (Clin. Exp. Immunol. 2001). More recently, independent groups have reported CD200 overexpression associated with multiple myeloma, AML, and CLL. In this study we investigated the in vitro effect of blockade of CD200 expression, using both anti‐CD200 mAbs and CD200‐specific siRNAs, on CTL induction in human PBL using a CD200+ lymphoma cell line (ly5). We found that blockade of CD200 on ly5 cells significantly enhanced anti‐tumor CTL responses in vitro. Production of the inflammatory cytokines TNFa and IFNg were similarly enhanced. Cell depletion studies supported an important role for antigen presenting cells in CD200 regulation of anti‐tumor responses. We also developed a CD200 ELISA assay to measure serum CD200 levels in healthy donor controls and cancer patients, and in preliminary analyses found elevated levels of sCD200 in the plasma of patients with CLL. Our data provide novel insights into the mechanisms of CD200 mediated suppression of tumor immunity, the understanding of which may open new avenues to development of different cancer therapies.