INVITED SPEAKERS ABSTRACTS
An update on UV-induced carcinogenesis
Skin cancers induced by UV irradiation constitute the most frequently detected malignancies in humans. UV irradiation does not only induce skin cancer by its direct mutagenic effects but also by suppressing cell-mediated immune responses. It has been hypothesized that UV-induced regulatory T cells play an important role in the downregulation of protective antitumoral immunity. However, the molecular mechanism by which UV is coupled to the immune system is largely unknown. Recently, we were able to demonstrate that epidermal expression of RANKL (CD254) induces Langerhans cells to expand regulatory T cells via CD205/CD86 in skin-draining lymph nodes. The suppressive effects of UV-induced regulatory T cells are partially mediated by CD80/CD86 signaling since treatment of chronically UV irradiated mice with neutralizing anti-CTLA-4 antibodies significantly reduced photocarcinogenesis. Another mediator of suppression by UV-induced regulatory T cells is the production of IL-10. Interestingly, IL-10-deficient mice showed strongly reduced development of UV-induced skin tumors compared to wild-type controls suggesting that IL-10 does indeed play an important role in UV-induced carcinogenesis. Additionally, UV-induced regulatory T cells from IL-10-deficient mice were inferior suppressors of conventional T cells compared to wild-type controls. Together, these data indicate that blocking CD80CD86-CTLA-4 signaling by anti-CTLA-4 antibodies or inhibition of IL-10 production induces immune protection against the development of UV-induced skin tumors. These experimental data furthermore establish the rationale for preventing photocarcinogenesis by interfering with CTLA-4- or IL-10 signaling.© 2010 Lippincott Williams & Wilkins, Inc.