title: Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer.
abstract: Interleukin-17 (IL-17) and IL-22 have been reported to play critical roles in autoimmunity and inflammation but information about their role in cancer is limited. In this study, we investigated the role of IL-17 and IL-22 in the progression of human skin basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). We found that both tumor types are infiltrated with an high number of IL-17(+) and IL-22(+) T lymphocytes, as demonstrated by immunohistochemistry and by FACS analysis performed on peritumoral T-cell lines isolated from skin biopsies. In vitro studies demonstrated that proliferation and migration of the BCC- and SCC-cell lines M77015 and CAL27 were increased by IL-17 and IL-22. Moreover, IL-17, alone or in combination with TNF-α, was able to induce the production of two cytokines important for tumor progression, IL-6 and IL-8, in CAL27. We also showed that IL-17 upregulated NF-κB signaling, while IL-22 activated the STAT3 pathway and the antiapoptotic AKT protein in M77015 and CAL27. Finally, in vivo experiments demonstrated that IL-17 and IL-22 enhanced tumor growth in nude mice injected with CAL27. Altogether, our findings indicate that high levels of IL-22 and IL-17 in the BCC and SCC microenvironment promote tumor progression.
authors.affiliation: Laboratory of Experimental Immunology, Istituto Dermopatico dell'Immacolata, Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Nardinocchi
authors.forename: Giulio
authors.initials: G
authors.lastname: Sonego
authors.forename: Francesca
authors.initials: F
authors.lastname: Passarelli
authors.forename: Simona
authors.initials: S
authors.lastname: Avitabile
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarponi
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Failla
authors.forename: Stefano
authors.initials: S
authors.lastname: Simoni
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000097043:Interleukin-22; C508606:CXCL8 protein, human; C508600:IL6 protein, human
keywords: IL-17; IL-22; T cells; cancer; dermatology