Interleukin-17 inhibits tumor cell growth by means of a T-cell–dependent mechanism

Benchetrit, Fabrice; Cirée, Arnaud; Vives, Virginie; Warnier, Guy; Gey, Alain; Sautès-Fridman, Catheriné; Fossiez, François; Haicheur, Nacilla; Fridman, Wolf H.; Tartour, Éric

doi:10.1182/blood.v99.6.2114

Cited by 309 publications

(263 citation statements)

References 49 publications

Supporting

Mentioning

247

Contrasting

Unclassified

Order By: Relevance

“…Conflicting data have been reported regarding the capacity of IL-23 and IL-17 to favour or inhibit cancer growth (Benchetrit et al, 2002;Langowski et al, 2006;Numasaki et al, 2003). We found that the overall expression of the genes encoding these factors is weak in prostate specimens, but nevertheless similar in BPH and PCA (Steiner et al, 2003).…”

Section: Discussionmentioning

confidence: 76%

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

Feder-Mengus¹,

Wyler²,

Hudolin³

et al. 2008

European Journal of Cancer

View full text Add to dashboard Cite

Arginase 2, inducible-and endothelial-nitric-oxide synthase (iNOS and eNOS), indoleamine 2,3-dioxygenase (IDO) and TGF-beta, might impair immune functions in prostate cancer (PCA) patients. However, their expression was not comparatively analysed in PCA and benign prostatic hyperplasia (BPH). We evaluated the expression of these genes in PCA and BPH tissues. Seventy-six patients (42 BPH, 34 PCA) were enrolled. Arginase 2, eNOS and iNOS gene expression was similar in BPH and PCA tissues. TGF-beta1 gene expression was higher in BPH than in PCA tissues (p=0.035). IDO gene expression was more frequently detectable (p=0.00007) and quantitatively higher (p=0.00001) in PCA tissues than in BPH. IDO protein, expressed in endothelial cells from both BPH and PCA, was detectable in tumour cells in PCA showing evidence of high specific gene expression. In these patients, IDO gene expression correlated with kynurenine/tryptophan ratio in sera. Thus high expression of IDO gene is specifically detectable in PCA. 1 High expression of indoleamine 2,3-dioxygenase gene in prostate cancerChantal FEDER-MENGUS 1 * and Stephen WYLER 1 * , Tvrtko HUDOLIN 2 , Robin RUSZAT 1 , Lukas BUBENDORF 3 , Alberto CHIARUGI 4 , Maria PITTELLI 4 , Walter P. Seventy-six patients, 42 BPH and 34 PCA, were enrolled. Expression of arginase 2, eNOS and iNOS genes was similar in BPH and PCA tissues. TGF-β1 gene expression was significantly higher in BPH than in PCA tissues (p=0.035). In contrast IDO gene expression was more frequently detectable in PCA as compared to BPH (p=0.00007). Its extent was also significantly higher in PCA than in BPH (p=0.00001).Immunohistochemistry revealed IDO protein in endothelial cells from both BPH and PCA. However, in PCA showing evidence of high specific gene expression, IDO was detectable in tumor cells as well. In patients bearing these tumors, IDO gene expression correlated with kynurenine/tryptophan ratio in sera.These data indicate that while genes encoding Arginase 2, iNOS, eNOS and TGF-β immunosuppressive factors are expressed in PCA and BPH, high expression of IDO gene is only detectable in PCA.

show abstract

Section: Discussionmentioning

confidence: 76%

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

Feder-Mengus¹,

Wyler²,

Hudolin³

et al. 2008

European Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Inhibitory titers correspond to the serum dilution that reduces the induced IL-6 secretion by 50%. When indicated, supernatant of the J558L cell line transfected with a cDNA encoding mIL-17A was used as a source of natural glycosylated IL-17A (a kind gift of Dr E. Tartour, Paris, France) [36].…”

Section: Assesment Of Anti-il-17 Inhibitory Ab In Vitromentioning

confidence: 99%

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

2006

View full text Add to dashboard Cite

IL-17 has been associated with multiple inflammatory disorders such as rheumatoid arthritis, asthma and multiple sclerosis. As these diseases require long-term treatment we turned to an auto-vaccine strategy for IL-17 neutralization in vivo. Mouse IL-17A was covalently linked to ovalbumin and used to immunize C57BL/6 mice. This vaccine induced the production of antibodies that blocked IL-17A bioactivity in vitro but did not react with the other IL-17 isoforms, including IL-17F. As the half-life of the Ab titers after the last immunogen administration was approximately 4 months, the vaccine provides for long lasting and selective inhibition of IL-17A activity in vivo. A monoclonal Ab (mAb) derived from these mice showed the same specificity for IL-17A. To test the ability of the vaccine to confer protection against an IL-17-dependent disorder, SJL mice were vaccinated with IL-17-OVA and encephalomyelitis (EAE) was induced by proteolipid protein (PLP) peptide 139-151. Vaccinated mice were completely protected against the disease. The above-mentioned anti-IL-17A mAb also prevented EAE development. The absence of clinical symptoms contrasted with unaltered PLP-induced cytokine production in vitro and unmodified anti-PLP IgG titers and isotypes. These results suggest that an anti-IL-17A auto-vaccine offers new perspectives for therapy of autoimmune diseases.

show abstract

“…18 -23 In previous studies, we have demonstrated that human tumors transfected with IL-17 showed increased growth in nude mice, whereas immunogenic tumors were inhibited in immunocompetent mice by means of a T-cell-dependent mechanism. 12,24 In all these studies, IL-17 was not naturally produced by the tumors but overexpressed secondary to the transfection of cells. In order to address the relevance of these models in tumors spontaneously occurring in humans, we look for the natural expression of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS), which are primary epidermotropic cutaneous T-cell lymphomas (CTCL).…”

mentioning

confidence: 99%

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

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

Self Cite

101

View full text Add to dashboard Cite

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.

show abstract

Interleukin-17 inhibits tumor cell growth by means of a T-cell–dependent mechanism

Cited by 309 publications

References 49 publications

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

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

Contact Info

Product

Resources

About