Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome).
Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.
Institut Biomédical des Cordeliers, Institut National de la Santé et de la Recherche Médicale, INSERM U255, Paris, France.
Arnaud
A
Cirée
Laurence
L
Michel
Sophie
S
Camilleri-Bröet
Francette
F
Jean Louis
Michèle
M
Oster
Beatrice
B
Flageul
Patricia
P
Senet
Francois
F
Fossiez
Wolf H
WH
Fridman
Hervé
H
Bachelez
Eric
E
Tartour
D001706:Biopsy; D002455:Cell Division; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D009182:Mycosis Fungoides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020381:Interleukin-17