Abstract
Peripheral blood cells from 28 patients with leukemic cutaneous T-cell lymphoma including 25 patients with Sezary syndrome were evaluated for expression of regulatory T-cell-associated markers (FoxP3, CD25, CTLA-4, neurophilin-1), T-cell activation markers (CD28 and its ligands B7.1 and B7.2) and NK cell-associated markers (NKG2D and its ligands Mic-A and Mic-B) using real-time quantitative polymerase chain reaction. T-plastin served as a positive genetic marker, and its expression correlated to blood tumor burden. More than 90% of samples had transcripts for CD28 and Mic-B, but less than 30% of samples expressed FoxP3, CTLA-4 and CD25. Expression of Mic-B by neoplastic cells could provide another mechanism to inhibit anti-tumor immune responses. FoxP3 expression correlated with a poor prognosis. Although the underlying mechanisms accounting for this correlation remain unclear, the expression of the Foxp3 and CTLA-4 regulatory elements indicates that a subset of leukemic cases displays a regulatory T-cell phenotype.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / metabolism
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B7-2 Antigen / genetics
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B7-2 Antigen / metabolism
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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CD28 Antigens / genetics
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CD28 Antigens / metabolism
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CTLA-4 Antigen
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Cohort Studies
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Forkhead Transcription Factors / genetics*
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Forkhead Transcription Factors / metabolism
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Gene Expression Profiling
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism
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Humans
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Lymphoma, T-Cell, Cutaneous / genetics*
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Lymphoma, T-Cell, Cutaneous / metabolism
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Lymphoma, T-Cell, Cutaneous / pathology
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Microfilament Proteins / genetics*
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Microfilament Proteins / metabolism
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NK Cell Lectin-Like Receptor Subfamily K
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Neurophysins / genetics
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Neurophysins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Receptors, Natural Killer Cell
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Sezary Syndrome / genetics
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Sezary Syndrome / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / pathology*
Substances
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Antigens, CD
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B7-2 Antigen
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Biomarkers, Tumor
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CD28 Antigens
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CD86 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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FOXP3 protein, human
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Forkhead Transcription Factors
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Histocompatibility Antigens Class I
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KLRK1 protein, human
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MICB antigen
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Membrane Glycoproteins
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Microfilament Proteins
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NK Cell Lectin-Like Receptor Subfamily K
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Neurophysins
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RNA, Messenger
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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plastin