FOXP3+CD25- tumor cells with regulatory function in Sézary syndrome.
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-Vbeta-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.
Heid
Julia B
JB
Tumor Immunology Program, Division of Immunogenetics (D030), German Cancer Research Center, Heidelberg, Germany.
Schmidt
Angelika
A
Oberle
Nina
N
Goerdt
Sergij
S
Krammer
Peter H
PH
Suri-Payer
Elisabeth
E
Klemke
Claus-Detlev
CD
D014408:Biomarkers, Tumor; D002478:Cells, Cultured; D019175:DNA Methylation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics* / Q000378:metabolism; D009182:Mycosis Fungoides / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D010641:Phenotype; D011379:Prognosis; D011565:Psoriasis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012751:Sezary Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology*
D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit