TY - JOUR A1 - Schatton, Tobias A1 - Yang, Jun A1 - Kleffel, Sonja A1 - Uehara, Mayuko A1 - Barthel, Steven R. A1 - Schlapbach, Christoph A1 - Zhan, Qian A1 - Dudeney, Stephen A1 - Mueller, Hansgeorg A1 - Lee, Nayoung A1 - de Vries, Juliane C. A1 - Meier, Barbara A1 - Beken, Seppe Vander A1 - Kluth, Mark A. A1 - Ganss, Christoph A1 - Sharpe, Arlene H. A1 - Waaga-Gasser, Ana Maria A1 - Sayegh, Mohamed H. A1 - Abdi, Reza A1 - Scharffetter-Kochanek, Karin A1 - Murphy, George F. A1 - Kupper, Thomas S. A1 - Frank, Natasha Y. A1 - Frank, Markus H. T1 - ABCB5 Identifies Immunoregulatory Dermal Cells JF - Cell Reports N2 - Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5\(^+\) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5\(^+\) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy. KW - mesenchymal stem cells KW - P-glycoprotein KW - regulatory T cells KW - maintain immune homeostasis KW - malignant melanoma KW - in vivo KW - skin KW - generation KW - transplant KW - tolerance Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149989 VL - 12 SP - 1564 EP - 1574 ER - TY - JOUR A1 - Baur, Johannes A1 - Mathe, Katrin A1 - Gesierich, Anja A1 - Weyandt, Gerhard A1 - Wiegering, Armin A1 - Germer, Christoph-Thomas A1 - Gasser, Martin A1 - Pelz, Jörg O. W. T1 - Morbidity and oncologic outcome after saphenous vein-sparing inguinal lymphadenectomy in melanoma patients JF - World Journal of Surgical Oncology N2 - Background: Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. Methods: A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. Results: A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7%). The rate of lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. Conclusions: The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional. KW - malignant melanoma KW - inguinal lymph node dissection KW - regional recurrence KW - V. saphena magna Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157687 VL - 15 IS - 99 ER - TY - JOUR A1 - Spivey, Tara L. A1 - De Giorgi, Valeria A1 - Zhao, Yingdong A1 - Bedognetti, Davide A1 - Pos, Zoltan A1 - Liu, Qiuzhen A1 - Tomei, Sara A1 - Ascierto, Maria Libera A1 - Uccellini, Lorenzo A1 - Reinboth, Jennifer A1 - Chouchane, Lotfi A1 - Stroncek, David F. A1 - Wang, Ena A1 - Marincola, Francesco M. T1 - The stable traits of melanoma genetics: an alternate approach to target discovery JF - BMC Genomics N2 - Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number. Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis. Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy. KW - tumors KW - comparative genomic hybridization KW - coloteral cancer KW - prognostic relevance KW - aquired resistance KW - malignant melanoma KW - antigen expression KW - tissue microarray KW - cell carcinoma KW - T cells Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131992 VL - 13 IS - 156 ER -