Expression of CD200 on AML blasts directly suppresses memory T-cell function [Letter]

Coles, Steven, Hills, Robert Kerrin ORCID: https://orcid.org/0000-0003-0166-0062, Wang, Edward Chung Yern ORCID: https://orcid.org/0000-0002-2243-4964, Burnett, Alan Kenneth, Man, Stephen Tzekwung ORCID: https://orcid.org/0000-0001-9103-1686, Darley, Richard Lawrence ORCID: https://orcid.org/0000-0003-0879-0724 and Tonks, Alex ORCID: https://orcid.org/0000-0002-6073-4976 2012. Expression of CD200 on AML blasts directly suppresses memory T-cell function [Letter]. Leukemia 26 (9) , pp. 2148-2151. 10.1038/leu.2012.77

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Abstract

Previous studies have shown that immunosuppression in acute myeloid leukemia (AML) is associated with changes in the adaptive immune compartment. Such changes include the suppression of memory T-cell function1 and the suppression of Th1 cytokine (TNFα, IL-2 and IFNγ)-producing cells.2 A suppressed immune response in AML is associated with a worse patient outcome and increased risk of relapse,3 as well as increased risk of infection impairing patient recovery.4 The over-expression of the immunosuppressive ligand CD200 is also associated with an increased risk of relapse in AML (hazard ratio 1.7); an observation consistent with a hypothesis in which CD200 inhibits clearance of residual disease.5, 6 As memory T-cell responses are central for tumor immunosurveillance and contribute to prolonged molecular remission,7 we carried out this study to establish how these responses were affected in AML patients over-expressing CD200 (Supplemental Table S1). We initially investigated whether CD200 expression on AML blasts influenced CD8+ T-cell cytotoxic potential and the frequency of TNFα-, IL-2- and IFNγ-producing CD4+/CD8+ memory T-cells (Supplementary Materials and Methods and Supplemental Figure S1 for gating strategy). Using CD107a as a marker of cytotoxic function, AML cells were activated with PMA/ionomycin. We show that the frequency of CD107a+CD8+ memory T-cells was significantly reduced by ~50% for CD200hi patients when compared with CD200lo AML, demonstrating that cytotoxic memory T-cell activity was compromised in CD200hi patients (Figure 1a). Furthermore, the frequencies of TNFα-, IL-2- and IFNγ-producing CD4+ memory cells were also reduced by ~50% for CD200hi patients when compared with CD200lo AML (Figure 1b), significantly so in the case of IL-2 and IFNγ. Interestingly, CD200lo patients displayed a higher IFNγ response, not only with respect to CD200hi patients but also in comparison to healthy donors, suggesting a role for this cytokine in AML, which is attenuated by CD200. No difference was observed for TNFα-, IL-2- and IFNγ-producing CD8+ memory cells between CD200hi, CD200lo and healthy donors (data not shown). CD200 has also been reported to mediate suppression of the Th1 response in chronic lymphocytic leukemia as well as solid tumors,8, 9 suggesting that CD200-mediated Th1 suppression is a central mechanism in cancer immunomodulation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Nature Publishing Group
ISSN:	0887-6924
Date of First Compliant Deposit:	30 March 2016
Last Modified:	08 Nov 2023 20:43
URI:	https://orca.cardiff.ac.uk/id/eprint/37545

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