Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer

Lavinia Nardinocchi, Giulio Sonego, Francesca Passarelli, Simona Avitabile, Claudia Scarponi, Cristina Maria Failla, Stefano Simoni, Cristina Albanesi, Andrea Cavani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)922-931
Number of pages10
JournalEuropean Journal of Immunology
Volume45
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Cancer
  • Dermatology
  • IL-17
  • IL-22
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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