FOXP3+CD25− Tumor Cells with Regulatory Function in Sézary Syndrome

• Published in: Journal of investigative dermatology Vol. 129; no. 12; pp. 2875 - 2885
• Main Authors: Heid, Julia B., Schmidt, Angelika, Oberle, Nina, Goerdt, Sergij, Krammer, Peter H., Suri-Payer, Elisabeth, Klemke, Claus-Detlev
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-2009; Nature Publishing Group; Elsevier Limited
• Subjects: Biological and medical sciences; Biomarkers, Tumor; Cells, Cultured; Dermatology; DNA Methylation; Flow Cytometry; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Regulation, Neoplastic - immunology; Hematologic and hematopoietic diseases; Humans; Immune Tolerance - immunology; Interleukin-2 - genetics; Interleukin-2 Receptor alpha Subunit - genetics; Interleukin-2 Receptor alpha Subunit - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mycosis Fungoides - genetics; Mycosis Fungoides - immunology; Mycosis Fungoides - pathology; Neoplastic Cells, Circulating; Phenotype; Prognosis; Psoriasis - genetics; Psoriasis - immunology; Psoriasis - pathology; Sezary Syndrome - genetics; Sezary Syndrome - immunology; Sezary Syndrome - pathology; Skin - immunology; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - physiology; Skin disease; Chronic; Cutaneous hematologic disease; Cell function; Sezary syndrome; Dermatology; Lymphoproliferative syndrome; Malignant hemopathy; Non Hodgkin lymphoma; Peripheral T cell lymphoma; Tumor cell; Cancer
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2009.175

Cutaneous T-cell lymphoma (CTCL) has been suggested by in vitro experiments to represent a malignant CD4+ T-cell proliferation with a regulatory T-cell (Treg) phenotype (CD4+CD25+FOXP3+). We investigated percentages of FOXP3+ and CD25+ cells in the blood of 15 Sézary, 14 mycosis fungoides (MF), and 10 psoriasis (Pso) patients and 20 normal healthy donors (NHDs). We found similar numbers of FOXP3+ cells in MF (10.4% of blood CD4+ cells) and Pso (11.1%) patients and NHDs (9.8%). In 8 of 15 (53%) Sézary patients, significantly reduced percentages of FOXP3+ cells were seen in blood (2.9%) and skin (10.4%). Interestingly, 6 of 15 (40%) Sézary patients showed significantly increased percentages of FOXP3+ cells (39.7% (blood), 20.3% (skin)); however, these cells did not express CD25. In these latter patients, clone-specific TCR-Vβ-chain antibodies were used to demonstrate that these FOXP3+CD25− cells were monoclonal CTCL tumor cells. FOXP3+CD25− CTCL tumor cells showed a highly demethylated status of the foxp3 gene locus similar to Treg cells, and they were functionally able to suppress IL-2 mRNA induction in TCR-stimulated conventional T cells. Thus, FOXP3+CD25− CTCL tumor cells with functional features of Treg cells define a subgroup of Sézary patients who might carry a different prognosis and might require differential treatment.