Th17 cytokines in non-melanoma skin cancer

Abstract

T-helper-type 17 cytokines have been implicated in epithelial cancer progression at mucosal sites. In this issue of the European Journal of Immunology, Nardinocchi et al. [Eur. J. Immunol. 2015. 45: 922-931] show that the Th17 cytokines IL-17 and IL-22 can both signal to nonmelanoma skin cancer cells, inducing both cellular proliferation and enhanced migration of human basal cell carcinoma and squamous cell carcinoma cell lines in vitro. These cytokines were also shown to exacerbate tumor growth in mice injected with the squamous cell carcinoma line, CAL27. Thus, IL-17 and IL-22 may be key factors in skin cancer progression and may provide novel prognostic markers in nonmelanoma skin cancer.

Keywords: Cancer; IL-17; IL-22; Skin; T cells.

Figure 1. Roles of IL-17 and IL-22 play roles in non-melanoma skin cancer

Non-melanoma skin cells, such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), express receptors for IL-17 and IL-22 and Nardinocchi et al. [16] show that these factors can increase tumor cell proliferation and migration in vitro. The enhanced proliferation and migration of BCC and SCC cell lines in response to IL-17 and IL-22 is associated with the induction of IL-6 and IL-8. The recruitment of myeloid cells (CD11c⁺) may constitute one of the pro-tumorigenic mechanisms of action of Th17 cells. Th17 and Th22 cells are depicted in the figure, but the cellular source of their signature cytokines in skin cancer remains to be determined. Using xenograft assays, Nardinocchi et al. show that these cytokines also accelerate tumor growth in vivo. IL-17 treatment of the SCC cell line CAL 27 induced NF-κB signaling in these cells and IL-22 treatment activated the Erk1/2 and STAT3 signaling pathway, which may be responsible for tumor progression.