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Tumor Biology

, Volume 34, Issue 1, pp 531–542 | Cite as

Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia

  • Ali Memarian
  • Maryam Nourizadeh
  • Farimah Masoumi
  • Mina Tabrizi
  • Amir Hossein Emami
  • Kamran Alimoghaddam
  • Jamshid Hadjati
  • Mahroo Mirahmadian
  • Mahmood Jeddi-Tehrani
Research Article

Abstract

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.

Keywords

CD200 Acute myeloid leukemia T-reg Immunosuppression Disease progression 

Notes

Acknowledgments

This study was supported by a grant from Tehran University of Medical Sciences and Avicenna Research Institute.

Conflict of interest

None

Supplementary material

13277_2012_578_MOESM1_ESM.doc (100 kb)
Supplementary Table Major clinical and laboratory characteristics of AML patients (DOC 99.5 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Ali Memarian
    • 1
  • Maryam Nourizadeh
    • 1
  • Farimah Masoumi
    • 1
  • Mina Tabrizi
    • 2
  • Amir Hossein Emami
    • 3
  • Kamran Alimoghaddam
    • 4
  • Jamshid Hadjati
    • 1
  • Mahroo Mirahmadian
    • 1
  • Mahmood Jeddi-Tehrani
    • 5
  1. 1.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Clinic of Hematology and Oncology, Vali-Asr Hospital, School of MedicineTehran University of Medical SciencesTehranIran
  4. 4.Hematology, Oncology and Stem Cell Transplantation Research CenterTehran University of Medical Sciences, Shariati HospitalTehranIran
  5. 5.Monoclonal Antibody Research CenterAvicenna Research InstituteTehranIran

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