Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Abstract

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.

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

“…haematopoietic tumours in immunocompetent mice) [112,113] of tumours in experimental animals. Although the role of IL-17 in tumour biology is unclear and evidence remains conflicting, IL-17 can be detected in some (such as ovarian, skin and prostatic cancers) [114][115][116] but not all (e.g. acute myeloid leukaemia) [117] human tumours and one emerging theme is that, when present, it promotes angiogenesis [111,114], for example through the up-regulation of angiogenic factors such as CXCL1, CXCL5, CXCL6 and CXCL8 [118], thereby facilitating tumour growth and invasion.…”

Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

“…1 T-cell differentiation that is predominant in the skin lesions of MF patients, [13][14][15][16][17] it has been consistently reported that the percentage of forkhead box P3 positive (FoxP3 1 ) cells decreases with disease progression.…”

A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer

“…Previous reports have shown that both cutaneous T-cell lymphomas 6 and ovarian carcinomas 7 spontaneously secrete interleukin (IL)-17A and in a considerable proportion of ovarian tumours IL-17A expression correlates with increased vascularity. However, no report exists concerning a possible angiogenic role for IL-17A in non-small cell lung cancer (NSCLC) [8][9][10] .…”