TY - JOUR
T1 - Expression of IL-23/Th17-related cytokines in basal cell carcinoma and in the response to medical treatments
AU - Chiricozzi, Andrea
AU - Peris, Ketty
AU - Di Stefani, Alessandro
AU - Fargnoli, Maria Concetta
AU - Pellegrini, Cristina
AU - Orlandi, Augusto
AU - Costanza, Gaetana
AU - Piccioni, Antonella
AU - Di Cesare, Antonella
AU - Ferlosio, Amedeo
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Agricultural and Biological Sciences (all)
KW - Aminoquinolines
KW - Antineoplastic Agents
KW - Biochemistry, Genetics and Molecular Biology (all)
KW - Carcinoma, Basal Cell
KW - Cytokines
KW - Female
KW - Humans
KW - Interleukin-23
KW - Male
KW - Middle Aged
KW - Photochemotherapy
KW - RNA, Messenger
KW - Real-Time Polymerase Chain Reaction
KW - Skin Neoplasms
KW - Th17 Cells
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Agricultural and Biological Sciences (all)
KW - Aminoquinolines
KW - Antineoplastic Agents
KW - Biochemistry, Genetics and Molecular Biology (all)
KW - Carcinoma, Basal Cell
KW - Cytokines
KW - Female
KW - Humans
KW - Interleukin-23
KW - Male
KW - Middle Aged
KW - Photochemotherapy
KW - RNA, Messenger
KW - Real-Time Polymerase Chain Reaction
KW - Skin Neoplasms
KW - Th17 Cells
UR - http://hdl.handle.net/10807/113392
UR - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183415&type=printable
U2 - 10.1371/journal.pone.0183415
DO - 10.1371/journal.pone.0183415
M3 - Article
VL - 12
SP - e0183415-N/A
JO - PLoS One
JF - PLoS One
SN - 1932-6203
ER -