Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-12215 Wissenschaftlicher Artikel Panayotova-Dimitrova, Diana; Feoktistova, Maria; Ploesser, Michaela; Kellert, Beate; Hupe, Mike; Horn, Sebastian; Makarov, Roman; Jensen, Federico; Porubsky, Stefan; Schmieder, Astrid; Zenclussen, Ana Claudia; Marx, Alexander; Kerstan, Andreas; Geserick, Peter; He, You-Wen; Leverkus, Martin cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIP(fl/fl)-K14CreER(tam) mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation. 2013 397-408 Cell Reports 5 urn:nbn:de:bvb:20-opus-122155 10.1016/j.celrep.2013.09.035 Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie OPUS4-11772 Wissenschaftlicher Artikel Behr, Daniel S.; Peitsch, Wiebke K.; Hametner, Christian; Lasitschka, Felix; Houben, Roland; Schönhaar, Kathrin; Michel, Julia; Dollt, Claudia; Goebeler, Matthias; Marx, Alexander; Goerdt, Sergij; Schmieder, Astrid Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival. 2014 7610-7621 International Journal of Clinical and Experimental Pathology 7 11 urn:nbn:de:bvb:20-opus-117720 Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie