Expression of IL-23/Th17-related cytokines in basal cell carcinoma and in the response to medical treatments

Andrea Chiricozzi, Ketty Peris, Alessandro Di Stefani, Maria Concetta Fargnoli, Cristina Pellegrini, Augusto Orlandi, Gaetana Costanza, Antonella Piccioni, Antonella Di Cesare, Amedeo Ferlosio

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

Abstract

Several immune-related markers have been implicated in basal cell carcinoma (BCC) pathogenesis. The BCC inflammatory infiltrate is dominated by Th2 cytokines, suggesting a specific state of immunosuppression. In contrast, regressing BCC are characterized by a Th1 immune response with IFN-γ promoting a tumor suppressive activity. IL-23/Th17-related cytokines, as interleukin (IL)-17, IL-23 and IL-22, play a significant role in cutaneous inflammatory diseases, but their involvement in skin carcinogenesis is controversial and is poorly investigated in BCC. In this study we investigated the expression of IFN-γ, IL-17, IL-23 and IL-22 cytokines in BCC at the protein and mRNA level and their modulation during imiquimod (IMQ) treatment or photodynamic therapy (PDT). IFN-γ, IL-17, IL-23 and IL-22 levels were evaluated by immunohistochemistry and quantitative Real Time PCR in 41 histopatho-logically-proven BCCs (28 superficial and 13 nodular) from 39 patients. All BCC samples were analyzed at baseline and 19 of 41 also during medical treatment (9 with IMQ 5% cream and 10 with MAL-PDT). Association between cytokines expression and clinico-pathological variables was evaluated. Higher levels of IFN-γ, IL-17, IL-23 and IL-22 were found in BCCs, mainly in the peritumoral infiltrate, compared to normal skin, with the expression being correlated to the severity of the inflammatory infiltrate. IFN-γ production was higher in superficial BCCs compared to nodular BCCs, while IL-17 was increased in nodular BCCs. A significant correlation was found between IFN-γ and IL-17 expression with both cytokines expressed by CD4+ and CD8+ T-cells. An increase of all cytokines occurred during the inflammatory phase induced by IMQ and at the early time point of PDT treatment, with significant evidence for IFN-γ, IL-23, and IL-22. Our results confirm the role of IFN-γ and support the involvement of IL-23/Th17-related cytokines in BCC pathogenesis and in the inflammatory response during IMQ and MAL-PDT treatments.
Lingua originaleEnglish
pagine (da-a)e0183415-N/A
RivistaPLoS One
Volume12
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Agricultural and Biological Sciences (all)
  • Aminoquinolines
  • Antineoplastic Agents
  • Biochemistry, Genetics and Molecular Biology (all)
  • Carcinoma, Basal Cell
  • Cytokines
  • Female
  • Humans
  • Interleukin-23
  • Male
  • Middle Aged
  • Photochemotherapy
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Skin Neoplasms
  • Th17 Cells

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