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 language | English |
|---|---|
| Pages (from-to) | 922-931 |
| Number of pages | 10 |
| Journal | European Journal of Immunology |
| Volume | 45 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2015 |
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Keywords
- Cancer
- Dermatology
- IL-17
- IL-22
- T cells
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer. / Nardinocchi, Lavinia; Sonego, Giulio; Passarelli, Francesca; Avitabile, Simona; Scarponi, Claudia; Failla, Cristina Maria; Simoni, Stefano; Albanesi, Cristina; Cavani, Andrea.
In: European Journal of Immunology, Vol. 45, No. 3, 01.03.2015, p. 922-931.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer
AU - Nardinocchi, Lavinia
AU - Sonego, Giulio
AU - Passarelli, Francesca
AU - Avitabile, Simona
AU - Scarponi, Claudia
AU - Failla, Cristina Maria
AU - Simoni, Stefano
AU - Albanesi, Cristina
AU - Cavani, Andrea
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Dermatology
KW - IL-17
KW - IL-22
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84924455824&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924455824&partnerID=8YFLogxK
U2 - 10.1002/eji.201445052
DO - 10.1002/eji.201445052
M3 - Article
VL - 45
SP - 922
EP - 931
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 3
ER -