title: Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis.
abstract: Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin. The depletion of NK cells or LC caused an accumulation of DNA-damaged, natural killer group 2D-ligand (NKG2D-L) expressing keratinocytes and accelerated tumor growth. Notably, the secretion of TNFα mainly by LC promoted the recruitment of NK cells into the epidermis. Indeed, the TNFα-induced chemokines CCL2 and CXCL10 directed NK cells to DMBA-treated epidermis. Our findings reveal a novel mechanism how innate immune cells cooperate in the inhibition of cutaneous chemical carcinogenesis.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ortner
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Tripp
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Komenda
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dubrac
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Hermann
authors.affiliation: Section for Medical Biochemistry, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doppler
authors.affiliation: Department of Internal Medicine VI, Infectious Diseases, Immunology, Rheumatology & Pneumology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Piotr Z
authors.initials: PZ
authors.lastname: Tymoszuk
authors.affiliation: Biocerus , Utrecht, the Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz, Germany.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
keywords: Chemical carcinogenesis; Langerhans cells; NK cells; epidermis; immunosurveillance