AbstractInterleukin‐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. © 2004 Wiley‐Liss, Inc.