Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia
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Immunosuppression in acute myeloid leukemia (AML) is an important mechanism of tumor escape. CD200, as an immunosuppressive molecule, is overexpressed in some hematological malignancies and it has also been shown to be an independent prognostic factor in AML. In the current study, simultaneous CD200 expression and Foxp3+ regulatory T cell levels were investigated in Iranian patients with AML by flow cytometry. We also assessed the effect of CD200–CD200R blockade on Th1 and T-reg cytokine production and T cell proliferation in autologous AML- and monocyte-DC mixed lymphocyte reactions (MLRs). ELISA assay was performed to detect IL-2, IL-12, IFN-γ, IL-10, and TGF-β production in MLR supernatants. Expression of Foxp3, IL-10, and TGF-β mRNAs in MLRs were detected by real-time PCR. Our results demonstrated significant overexpression of CD200 (P = 0.001) in association with higher frequencies of Foxp3+ T cells in AML patients (r = 0.8, P < 0.001). Blocking of CD200–CD200R interaction demonstrated a significant decrease in TGF-β and IL-10 expression in AML-DC MLRs and a significant increase in IL-12 and IFN-γ expression in monocyte-DC MLRs. Elevated T cell levels with lower Foxp3 intensity was also shown in CD200–CD200R-blocked MLRs. Expression of IL-10 mRNA declined significantly only in AML-DC MLRs where CD200–CD200R interaction was blocked and the same result was observed for TGF-β and Foxp3 mRNA in both AML- and monocyte-DC MLRs. These data present a significant role for CD200 in suppressing anti-tumor immune response through stimulation of regulatory mechanisms in AML patients and suggest that CD200 may have a prognostic value in this malignancy and its blockade may be used as a target for AML immunotherapy.
KeywordsCD200 Acute myeloid leukemia T-reg Immunosuppression Disease progression
This study was supported by a grant from Tehran University of Medical Sciences and Avicenna Research Institute.
Conflict of interest
- 9.Delluc S, Hachem P, Rusakiewicz S, Gaston A, Marchiol-Fournigault C, Tourneur L, et al. Dramatic efficacy improvement of a DC-based vaccine against AML by CD25 T cell depletion allowing the induction of a long-lasting T cell response. Cancer Immunol Immunother. 2009;58(10):1669–77.PubMedCrossRefGoogle Scholar
- 14.Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J, Munn DH, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009;114(18):3793–802. doi: 10.1182/blood-2009-03-208181.PubMedCrossRefGoogle Scholar
- 54.Mahadevan D, Lanasa MC, Whelden M, Faas SJ, Ulery TL, Kukreja A, et al. First-in-human phase I dose escalation study of a humanized anti-CD200 antibody (Samalizumab) in patients with advanced stage B cell chronic lymphocytic leukemia (B-CLL) or multiple myeloma (MM). 52nd ASH Annual Meeting and Exposition. 2010; 2116: 2465Google Scholar