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CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia

Coles, Steven, Wang, Edward Chung Yern, Man, Stephen Tzekwung, Hills, Robert Kerrin, Burnett, Alan Kenneth, Tonks, Alex and Darley, Richard Lawrence 2011. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia. Leukemia 25 (5) , pp. 792-799. 10.1038/leu.2011.1

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Abstract

Upregulation of the immunosuppressive cell surface glycoprotein, CD200, is a common feature of acute myeloid leukemia (AML) and is associated with poor patient outcome. We investigated whether CD200 overexpression on AML cells could specifically compromise patient natural killer (NK) cell anti-tumor responses. We found that CD200hi patients showed a 50% reduction in the frequency of activated NK cells (CD56dimCD16+) compared with CD200lo patients. Additionally, NK receptor expression (NKp44 and NKp46) on these cells was also significantly downregulated in CD200hi patients. To assess whether NK cell activity was directly influenced by CD200 expression, we examined the effect of ectopic expression of CD200. These assays revealed that both NK cell cytolytic activity and interferon-γ response were significantly reduced toward CD200+ leukemic targets and that these targets showed increased survival compared with CD200− cells. Similarly, NK cells isolated from AML patients were less functionally active toward CD200hi autologous blasts from both cytolytic and immunoregulatory perspectives. Finally, blocking CD200 alone was sufficient to recover a significant proportion of NK cell cytolytic activity. Together, these findings provide the first evidence that CD200 has a direct and significant suppressive influence on NK cell activity in AML patients and may contribute to the increased relapse rate in CD200+ patients.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: CD200; natural killer cell; immunity; AML; CD200R; immunosuppression
Publisher: Nature Publishing Group
ISSN: 0887-6924
Last Modified: 19 Oct 2019 02:49
URI: http://orca-mwe.cf.ac.uk/id/eprint/26935

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