@article{WobserGoebeler2023,
  author    = {Wobser, Marion and Goebeler, Matthias},
  title     = {Special Issue "Cutaneous Lymphomas"},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15051481},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304180},
  year      = {2023},
  abstract  = {No abstract available},
  language  = {en}
}
@article{HaakeHaackSchaeferetal.2023,
  author    = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg},
  title     = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-39817-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333},
  year      = {2023},
  abstract  = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.},
  language  = {en}
}
@article{WobserWeberGlunzetal.2019,
  author    = {Wobser, Marion and Weber, Alexandra and Glunz, Amelie and Tauch, Saskia and Seitz, Kristina and Butelmann, Tobias and Hesbacher, Sonja and Goebeler, Matthias and Bartz, Ren{\´e} and Kohlhof, Hella and Schrama, David and Houben, Roland},
  title     = {Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells},
  series = {Journal of Hematology \& Oncology},
  volume    = {12},
  journal   = {Journal of Hematology \& Oncology},
  doi       = {10.1186/s13045-019-0719-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200703},
  pages     = {30},
  year      = {2019},
  abstract  = {Background Targeting epigenetic modifiers is effective in cutaneous T cell lymphoma (CTCL). However, there is a need for further improvement of this therapeutic approach. Here, we compared the mode of action of romidepsin (FK228), an established class I histone deacetylase inhibitor, and domatinostat (4SC-202), a novel inhibitor of class I HDACs, which has been reported to also target the lysine-specific histone demethylase 1A (LSD1). Methods We performed MTS assays and flow cytometric analyses of propidium iodide or annexin V-stained cells to assess drug impact on cellular proliferation, cell cycle distribution, and survival. Histone acetylation and methylation as well as caspase activation was analyzed by immunoblot. Gene expression analysis was performed using NanosString technology. Knockdown and knockout of LSD1 was achieved with shRNA and CRISPR/Cas9, respectively, while the CRISPR/Cas9 synergistic activation mediator system was used to induce expression of endogenous HDACs and LSD1. Furthermore, time-lapse fluorescence microscopy and an in vitro tubulin polymerization assay were applied. Results While FK228 as well as 4SC-202 potently induced cell death in six different CTCL cell lines, only in the case of 4SC-202 death was preceded by an accumulation of cells in the G2/M phase of the cell cycle. Surprisingly, apoptosis and accumulation of cells with double DNA content occurred already at 4SC-202 concentrations hardly affecting histone acetylation and methylation, and provoking significantly less changes in gene expression compared to biologically equivalent doses of FK228. Indeed, we provide evidence that the 4SC-202-induced G2/M arrest in CTCL cells is independent of de novo transcription. Furthermore, neither enforced expression of HDAC1 nor knockdown or knockout of LSD1 affected the 4SC-202-induced effects. Since time-lapse microscopy revealed that 4SC-202 could affect mitotic spindle formation, we performed an in vitro tubulin polymerization assay revealing that 4SC-202 can directly inhibit microtubule formation. Conclusions We demonstrate that 4SC-202, a drug currently tested in clinical trials, effectively inhibits growth of CTCL cells. The anti-cancer cell activity of 4SC-202 is however not limited to LSD1-inhibition, modulation of histone modifications, and consecutive alteration of gene expression. Indeed, the compound is also a potent microtubule-destabilizing agent.},
  language  = {en}
}
@article{FringsRothRosenwaldetal.2021,
  author    = {Frings, Verena G. and Roth, Sabine and Rosenwald, Andreas and Goebeler, Matthias and Geissinger, Eva and Wobser, Marion},
  title     = {EBER in situ hybridization in subcutaneous aluminum granulomas/lymphoid hyperplasia: A diagnostic clue to differentiate injection-associated lymphoid hyperplasia from other forms of pseudolymphomas and cutaneous lymphomas},
  series = {Journal of Cutaneous Pathology},
  volume    = {48},
  journal   = {Journal of Cutaneous Pathology},
  number    = {5},
  doi       = {10.1111/cup.13972},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258405},
  pages     = {625-631},
  year      = {2021},
  abstract  = {Background Subcutaneous vaccination or desensitization may induce persistent nodules at the injection sites. Without the knowledge of prior injection, histopathological work-up may be challenging. Objective Aim of this study was to contribute to the histopathological work-up of unclear subcutaneous nodules, especially their differentiation from cutaneous lymphoma. Methods We retrospectively reviewed clinical data and histopathological slides of four patients with subcutaneous nodules, which were suspected to suffer from cutaneous T- or B-cell lymphoma. Sections of these cases and 12 negative controls were stained with hematoxylin and eosin and a standardized immunohistochemical panel of B- and T-cell markers including EBER in situ hybridization as well as electron microscopy. Results In all cases, large histiocytes with granular cytoplasm compatible with intracellular aluminum hydroxide were present. EBER in situ hybridization revealed positive staining of these granular histiocytes while staining was absent in negative controls. Limitations Post hoc completion of medical history revealed that vaccination or specific immunotherapy had been applied before at the biopsy site in only three out of four patients; one patient was lost to follow-up. Conclusion EBER in situ hybridization is an adjunctive tool to differentiate aluminum-induced granuloma/lymphoid hyperplasia from other forms of pseudolymphoma and cutaneous B- or T-cell lymphomas.},
  language  = {en}
}
@article{GlutschSchummerKneitzetal.2022,
  author    = {Glutsch, Valerie and Schummer, Patrick and Kneitz, Hermann and Gesierich, Anja and Goebeler, Matthias and Klein, Detlef and Posch, Christian and Gebhardt, Christoffer and Haferkamp, Sebastian and Zimmer, Lisa and Becker, J{\"u}rgen C and Leiter, Ulrike and Weichenthal, Michael and Schadendorf, Dirk and Ugurel, Selma and Schilling, Bastian},
  title     = {Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG},
  series = {Journal for ImmunoTherapy of Cancer},
  volume    = {10},
  journal   = {Journal for ImmunoTherapy of Cancer},
  number    = {11},
  issn      = {2051-1426},
  doi       = {10.1136/jitc-2022-005930},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304613},
  year      = {2022},
  abstract  = {Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62\%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50\%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95\% CI 2.43—not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9\% and 26.8 \%, respectively. The OS rate at 36 months was 64.3\%. Only 3 (21\%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.},
  language  = {en}
}
@article{BumillerBiniHochKohlerAugustoetal.2022,
  author    = {Bumiller-Bini Hoch, Val{\´e}ria and Kohler, Ana Fl{\´a}via and Augusto, Danillo G. and Lobo-Alves, Sara Cristina and Malheiros, Danielle and Cipolla, Gabriel Adelman and Winter Boldt, Angelica Beate and Braun-Prado, Karin and Wittig, Michael and Franke, Andre and Pf{\"o}hler, Claudia and Worm, Margitta and van Beek, Nina and Goebeler, Matthias and S{\´a}rdy, Mikl{\´o}s and Ibrahim, Saleh and Busch, Hauke and Schmidt, Enno and Hundt, Jennifer Elisabeth and Araujo-Souza, Patr{\´i}cia Savio de and Petzl-Erler, Maria Luiza},
  title     = {Genetic associations and differential mRNA expression levels of host genes suggest a viral trigger for endemic pemphigus foliaceus},
  series = {Viruses},
  volume    = {14},
  journal   = {Viruses},
  number    = {5},
  issn      = {1999-4915},
  doi       = {10.3390/v14050879},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270572},
  year      = {2022},
  abstract  = {The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus-human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.},
  language  = {en}
}
@article{MohmeSchmalzingMuelleretal.2020,
  author    = {Mohme, Sophia and Schmalzing, Marc and M{\"u}ller, Cornelia S.L. and Vogt, Thomas and Goebeler, Matthias and Stoevesandt, Johanna},
  title     = {Immunizations in immunocompromised patients: a guide for dermatologists},
  series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {18},
  journal   = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {7},
  doi       = {10.1111/ddg.14156},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217982},
  pages     = {699 -- 723},
  year      = {2020},
  abstract  = {The increasingly frequent use of immunomodulatory agents in dermatology requires the observance of specific recommendations for immunization. These recommendations are developed and regularly updated by the German Standing Committee on Vaccination (STIKO), an independent advisory group at the Robert Koch Institute. Dermatological patients on immunosuppressive treatment should ideally receive all vaccinations included in the standard immunization schedule. Additionally, it is recommended that they also undergo vaccination against the seasonal flu, pneumococci, and herpes zoster (inactivated herpes zoster subunit vaccine for patients ≥ 50 years). Additional immunizations against Haemophilus influenzae type B, hepatitis B and meningococci may be indicated depending on individual comorbidities and exposure risk. Limitations of use, specific contraindications and intervals to be observed between vaccination and immunosuppression depend on the immunosuppressive agent used and its dosing. Only under certain conditions may live-attenuated vaccines be administered in patients on immunosuppressive therapy. Given its strong suppressive effect on the humoral immune response, no vaccines - except for flu shots - should be given within six months after rituximab therapy. This CME article presents current recommendations on immunization in immunocompromised individuals, with a special focus on dermatological patients. Its goal is to enable readers to provide competent counseling and to initiate necessary immunizations in this vulnerable patient group.},
  language  = {en}
}
@article{BenoitGoebeler2015,
  author    = {Benoit, Sandrine and Goebeler, Matthias},
  title     = {Mepacrine in recalcitrant cutaneous lupus erythematosus: old-fashioned or still useful?},
  series = {Acta Dermato-Venereologica},
  volume    = {95},
  journal   = {Acta Dermato-Venereologica},
  doi       = {10.2340/00015555-2031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149181},
  pages     = {596-599},
  year      = {2015},
  abstract  = {Treatment of recalcitrant cutaneous lupus erythematosus (CLE) is challenging. In situations where conventional treatment approaches fail mepacrine - an antimalarial/antiinfiammatory drug that has fallen into oblivion in the last decades might still be a promising option. We retrospectively analysed medical records of 10 patients with refractory CLE that were treated with mepacrine (100-200 mg/day) as mono- or combination therapy for various time intervals between 2001 and 2013 at the University Hospital Wurzburg. Mepacrine was generally well tolerated. Side effects were mild and usually resolved after reduction or cessation. Over 50\% of the patients experienced amelioration of their symptoms despite a previously recalcitrant clinical course. Altogether, our data demonstrate that mepacrine still remains a useful and effective therapeutic option for otherwise treatment-resistant CLE.},
  language  = {en}
}
@article{StoevesandtKeitaGoebeler2022,
  author    = {Stoevesandt, Johanna and Keita, Dyamilatou Ulrike and Goebeler, Matthias},
  title     = {Disease-related burden and long-term outcome in orofacial granulomatosis: observations from a large single-centre cohort},
  series = {Clinical and Experimental Dermatology},
  volume    = {47},
  journal   = {Clinical and Experimental Dermatology},
  number    = {6},
  doi       = {10.1111/ced.15124},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318412},
  pages     = {1169 -- 1173},
  year      = {2022},
  abstract  = {There is a lack of standardized treatment recommendations for orofacial granulomatosis, a chronic inflammatory condition aetiologically related to Crohn disease. To assess clinical baseline parameters and treatment strategies, we retrospectively analysed 61 consecutive cases from our institutional database. Disease-related functional/psychological impairment and long-term outcomes were descriptively evaluated using a standardized self-reporting questionnaire. The median age of patients was 45 (7-77) years. Oral steroids were given in 41.0\% of cases, but only produced short-term disease control, while response to steroid-sparing agents was inconsistent. Only a minority of patients reported relevant disease-related functional impairment in eating (21.7\%) or speaking (4.3\%), but the majority perceived psychological distress due to the cosmetic aspects of the disease (69.6\%), comments from others (65.2\%) and/or general anxiety/insecurity (73.9\%). Regardless of the initial treatment, long-term outcomes after 71 months (range 7-304 months) were beneficial, with most patients being in complete remission (52.2\%) or reporting only mild residual swelling (43.5\%).},
  language  = {en}
}
@article{StrobelSickenbergerSchoenetal.2022,
  author    = {Strobel, Katharina and Sickenberger, Christina and Schoen, Christoph and Kneitz, Hermann and Kolb-M{\"a}urer, Annette and Goebeler, Matthias},
  title     = {Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis},
  series = {Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {20},
  journal   = {Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {9},
  doi       = {10.1111/ddg.14847},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318428},
  pages     = {1211 -- 1218},
  year      = {2022},
  abstract  = {Background and Objectives In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions. Patients and Methods Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital W{\"u}rzburg and considered for detailed analysis. Results Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up. Conclusions Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.},
  language  = {en}
}
@article{FringsGoebelerSchillingetal.2021,
  author    = {Frings, Verena Gerlinde and Goebeler, Matthias and Schilling, Bastian and Kneitz, Hermann},
  title     = {Aberrant cytoplasmic connexin43 expression as a helpful marker in vascular neoplasms},
  series = {Journal of Cutaneous Pathology},
  volume    = {48},
  journal   = {Journal of Cutaneous Pathology},
  number    = {11},
  doi       = {10.1111/cup.14066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258412},
  pages     = {1335-1341},
  year      = {2021},
  abstract  = {Background Gap junctions consisting of connexins (Cx) are fundamental in controlling cell proliferation, differentiation, and cell death. Cx43 is the most broadly expressed Cx in humans and is attributed an important role in skin tumor development. Its role in cutaneous vascular neoplasms is yet unknown. Methods Fifteen cases each of cutaneous angiosarcoma (cAS), Kaposi sarcoma (KS), and cherry hemangioma (CH) were assessed by immunohistochemistry for expression of Cx43. Expression pattern, intensity, and percentage of positively stained cells were analyzed. Solid basal cell carcinomas served as positive and healthy skin as negative controls. Results Most cases of cAS presented with a strong Cx43 staining of almost all tumor cells, whereas endothelia of KS showed medium expression and CH showed mostly weak expression. In comparison with KS or cAS, the staining intensity of CH was significantly lower (P ≤ 0.001). All tissue sections of both cAS and KS were characterized by a mostly diffuse, cytoplasmic staining pattern of the vascular endothelia. None of those showed nuclear staining. Conclusion The high-to-intermediate expression of Cx43 observed in all cases of cAS and KS suggests that this Cx may play a role in the development of malignant vascular neoplasms and serve as a helpful diagnostic marker.},
  language  = {en}
}
@article{WobserRothAppenzelleretal.2021,
  author    = {Wobser, Marion and Roth, Sabine and Appenzeller, Silke and Houben, Roland and Schrama, David and Goebeler, Matthias and Geissinger, Eva and Rosenwald, Andreas and Maurus, Katja},
  title     = {Targeted deep sequencing of mycosis fungoides reveals intracellular signaling pathways associated with aggressiveness and large cell transformation},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {21},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13215512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250094},
  year      = {2021},
  abstract  = {Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). The analyzed patients were attributed to three different groups based on the presence of LCT and clinical behavior. Results: While indolent MF cases without LCT did not show pathogenic driver mutations, a high rate of oncogenic alterations was detected in patients with LCT and aggressive clinical courses. Various genes of different oncogenic signaling pathways, including the MAPK and JAK-STAT signaling pathways, as well as epigenetic modifiers were affected. A high inter-individual and distinctive intra-individual mutation diversity was observed. Oncogenic RAS mutations were exclusively detected in patients with LCT. Conclusion: Our data demonstrate that LCT transition of MF is associated with increased frequency of somatic mutations in cancer-associated genes. In particular, the activation of RAS signaling — together with epigenetic dysregulation — may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior.},
  language  = {en}
}
@article{GlutschGraenWeberetal.2019,
  author    = {Glutsch, Valerie and Gr{\"a}n, Franziska and Weber, Judith and Gesierich, Anja and Goebeler, Matthias and Schilling, Bastian},
  title     = {Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy},
  series = {Journal for ImmunoTherapy of Cancer},
  volume    = {7},
  journal   = {Journal for ImmunoTherapy of Cancer},
  doi       = {10.1186/s40425-019-0655-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201214},
  pages     = {181},
  year      = {2019},
  abstract  = {Background High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined checkpoint inhibition. In BRAF wildtype patients with a primary resistance to PD-1 inhibitors, therapeutic options are therefore limited and immune-related adverse events (irAE) have to be taken into consideration when discussing a subsequent immunotherapy. Case presentation We report the case of a 68-year-old male patient with metastatic melanoma who experienced an acute renal failure with nephrotic syndrome due to a minimal change disease developing after a single dose of the anti-PD-1 antibody pembrolizumab. A kidney biopsy revealed a podocytopathy without signs of interstitial nephritis. Renal function recovered to almost normal creatinine and total urine protein levels upon treatment with oral steroids and diuretics. Unfortunately, a disease progression (PD, RECIST 1.1) was observed in a CT scan after resolution of the irAE. In a grand round, re-exposure to a PD-1-containing regime was recommended. Consensually, a combined immunotherapy with ipilimumab and nivolumab was initiated. Nephrotoxicity was tolerable during combined immunotherapy and a CT scan of chest and abdomen showed a deep partial remission (RECIST 1.1) after three doses of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Conclusion This case illustrates that a fulminant response to combined checkpoint inhibition is possible after progression after anti-PD-1 monotherapy and a severe irAE.},
  language  = {en}
}
@article{HoeslFroehlichPoschetal.2021,
  author    = {Hoesl, Christine and Fr{\"o}hlich, Thomas and Posch, Christian and Kneitz, Hermann and Goebeler, Matthias and Schneider, Marlon R. and Dahlhoff, Maik},
  title     = {The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis},
  series = {Molecular Oncology},
  volume    = {15},
  journal   = {Molecular Oncology},
  number    = {8},
  doi       = {10.1002/1878-0261.12945},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238925},
  pages     = {2140 -- 2155},
  year      = {2021},
  abstract  = {The incidence of melanoma and nonmelanoma skin cancer has increased tremendously in recent years. Although novel treatment options have significantly improved patient outcomes, the prognosis for most patients with an advanced disease remains dismal. It is, thus, imperative to understand the molecular mechanisms involved in skin carcinogenesis in order to develop new targeted treatment strategies. Receptor tyrosine kinases (RTK) like the ERBB receptor family, including EGFR/ERBB1, ERBB2/NEU, ERBB3, and ERBB4, are important regulators of skin homeostasis and their dysregulation often results in cancer, which makes them attractive therapeutic targets. Members of the leucine-rich repeats and immunoglobulin-like domains protein family (LRIG1-3) are ERBB regulators and thus potential therapeutic targets to manipulate ERBB receptors. Here, we analyzed the function of LRIG1 during chemically induced skin carcinogenesis in transgenic mice expressing LRIG1 in the skin under the control of the keratin 5 promoter (LRIG1-TG mice). We observed a significant induction of melanocytic tumor formation in LRIG1-TG mice and no difference in papilloma incidence between LRIG1-TG and control mice. Our findings also revealed that LRIG1 affects ERBB signaling via decreased phosphorylation of EGFR and increased activation of the oncoprotein ERBB2 during skin carcinogenesis. The epidermal proliferation rate was significantly decreased during epidermal tumorigenesis under LRIG1 overexpression, and the apoptosis marker cleaved caspase 3 was significantly activated in the epidermis of transgenic LRIG1 mice. Additionally, we detected LRIG1 expression in human cutaneous squamous cell carcinoma and melanoma samples. Therefore, we depleted LRIG1 in human melanoma cells (A375) by CRISPR/Cas9 technology and found that this caused EGFR and ERBB3 downregulation in A375 LRIG1 knockout cells 6 h following stimulation with EGF. In conclusion, our study demonstrated that LRIG1-TG mice develop melanocytic skin tumors during chemical skin carcinogenesis and a deletion of LRIG1 in human melanoma cells reduces EGFR and ERBB3 expression after EGF stimulation.},
  language  = {en}
}
@article{RauschenbergerSchmittAzeemetal.2019,
  author    = {Rauschenberger, Tabea and Schmitt, Viola and Azeem, Muhammad and Klein-Hessling, Stefan and Murti, Krisna and Gr{\"a}n, Franziska and Goebeler, Matthias and Kerstan, Andreas and Klein, Matthias and Bopp, Tobias and Serfling, Edgar and Muhammad, Khalid},
  title     = {T cells control chemokine secretion by keratinocytes},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {1917},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2019.01917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195695},
  year      = {2019},
  abstract  = {The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible "defense genes" in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.},
  language  = {en}
}
@article{AlrefaiMuhammadRudolfetal.2016,
  author    = {Alrefai, Hani and Muhammad, Khalid and Rudolf, Ronald and Pham, Duong Anh Thuy and Klein-Hessling, Stefan and Patra, Amiya K. and Avots, Andris and Bukur, Valesca and Sahin,, Ugur and Tenzer, Stefan and Goebeler, Matthias and Kerstan, Andreas and Serfling, Edgar},
  title     = {NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells},
  series = {Nature Communications},
  volume    = {7},
  journal   = {Nature Communications},
  doi       = {10.1038/ncomms11724},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173053},
  year      = {2016},
  abstract  = {Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.},
  language  = {en}
}
@article{ThiemHesbacherKneitzetal.2019,
  author    = {Thiem, Alexander and Hesbacher, Sonja and Kneitz, Hermann and di Primio, Teresa and Heppt, Markus V. and Hermanns, Heike M. and Goebeler, Matthias and Meierjohann, Svenja and Houben, Roland and Schrama, David},
  title     = {IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression},
  series = {Journal of Experimental \& Clinical Cancer Research},
  volume    = {38},
  journal   = {Journal of Experimental \& Clinical Cancer Research},
  doi       = {10.1186/s13046-019-1403-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201016},
  pages     = {397},
  year      = {2019},
  abstract  = {Background Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associated with better clinical response and increased survival to anti-PD-1 therapy. Moreover, there is increasing evidence that tumor suppressor proteins are involved in immune regulation and are capable of modulating the expression of immune checkpoint proteins. Here, we determined the role of p53 protein (gene name: TP53) in the regulation of PD-L1 expression in melanoma. Methods We analyzed publicly available mRNA and protein expression data from the cancer genome/proteome atlas and performed immunohistochemistry on tumors with known TP53 status. Constitutive and IFN-ɣ-induced PD-L1 expression upon p53 knockdown in wildtype, TP53-mutated or JAK2-overexpressing melanoma cells or in cells, in which p53 was rendered transcriptionally inactive by CRISPR/Cas9, was determined by immunoblot or flow cytometry. Similarly, PD-L1 expression was investigated after overexpression of a transcriptionally-impaired p53 (L22Q, W23S) in TP53-wt or a TP53-knockout melanoma cell line. Immunoblot was applied to analyze the IFN-ɣ signaling pathway. Results For TP53-mutated tumors, an increased CD274 mRNA expression and a higher frequency of PD-L1 positivity was observed. Interestingly, positive correlations of IFNG mRNA and PD-L1 protein in both TP53-wt and -mutated samples and of p53 and PD-L1 protein suggest a non-transcriptional mode of action of p53. Indeed, cell line experiments revealed a diminished IFN-ɣ-induced PD-L1 expression upon p53 knockdown in both wildtype and TP53-mutated melanoma cells, which was not the case when p53 wildtype protein was rendered transcriptionally inactive or by ectopic expression of p53\(^{L22Q,W23S}\), a transcriptionally-impaired variant, in TP53-wt cells. Accordingly, expression of p53\(^{L22Q,W23S}\) in a TP53-knockout melanoma cell line boosted IFN-ɣ-induced PD-L1 expression. The impaired PD-L1-inducibility after p53 knockdown was associated with a reduced JAK2 expression in the cells and was almost abrogated by JAK2 overexpression. Conclusions While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy.},
  language  = {en}
}
@article{FusiPaudelMederetal.2022,
  author    = {Fusi, Lorenza and Paudel, Rupesh and Meder, Katharina and Schlosser, Andreas and Schrama, David and Goebeler, Matthias and Schmidt, Marc},
  title     = {Interaction of transcription factor FoxO3 with histone acetyltransferase complex subunit TRRAP modulates gene expression and apoptosis},
  series = {Journal of Biological Chemistry},
  volume    = {298},
  journal   = {Journal of Biological Chemistry},
  number    = {3},
  doi       = {10.1016/j.jbc.2022.101714},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299820},
  year      = {2022},
  abstract  = {Forkhead box O (FoxO) transcription factors are conserved proteins involved in the regulation of life span and age-related diseases, such as diabetes and cancer. Stress stimuli or growth factor deprivation promotes nuclear localization and activation of FoxO proteins, which—depending on the cellular context—can lead to cell cycle arrest or apoptosis. In endothelial cells (ECs), they further regulate angiogenesis and may promote inflammation and vessel destabilization implicating a role of FoxOs in vascular diseases. In several cancers, FoxOs exert a tumor-suppressive function by regulating proliferation and survival. We and others have previously shown that FoxOs can regulate these processes via two different mechanisms: by direct binding to forkhead-responsive elements at the promoter of target genes or by a poorly understood alternative process that does not require direct DNA binding and regulates key targets in primary human ECs. Here, we performed an interaction study in ECs to identify new nuclear FoxO3 interaction partners that might contribute to FoxO-dependent gene regulation. Mass spectrometry analysis of FoxO3-interacting proteins revealed transformation/transcription domain-associated protein (TRRAP), a member of multiple histone acetyltransferase complexes, as a novel binding partner of FoxO family proteins. We demonstrate that TRRAP is required to support FoxO3 transactivation and FoxO3-dependent G1 arrest and apoptosis in ECs via transcriptional activation of the cyclin-dependent kinase inhibitor p27\(^{kip1}\) and the proapoptotic B-cell lymphoma 2 family member, BIM. Moreover, FoxO-TRRAP interaction could explain FoxO-induced alternative gene regulation via TRRAP-dependent recruitment to target promoters lacking forkhead-responsive element sequences.},
  language  = {en}
}
@article{HeitmannFringsGeieretal.2021,
  author    = {Heitmann, Johanna and Frings, Verena G. and Geier, Andreas and Goebeler, Matthias and Kerstan, Andreas},
  title     = {Non-alcoholic fatty liver disease and psoriasis - is there a shared proinflammatory network?},
  series = {Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {19},
  journal   = {Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {4},
  doi       = {10.1111/ddg.14425},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258424},
  pages     = {517-528},
  year      = {2021},
  abstract  = {Psoriasis is an immune-mediated systemic inflammatory disease that is not limited to the skin but may be associated with arthritis, cardiovascular diseases, metabolic syndrome including diabetes and obesity and, as identified more recently, non-alcoholic fatty liver disease (NAFLD) that occurs in approximately 50 \% of all patients with psoriasis. NAFLD is characterized by accumulation of fat in hepatocytes in the absence of excessive alcohol consumption. Over the last two decades, NAFLD has developed to the most common chronic liver disease with an estimated prevalence of 25 \% in the Western population. NAFLD ranges from non-inflammatory or bland hepatic steatosis to inflammation of hepatic tissue (non-alcoholic steatohepatitis, NASH) and consecutive liver fibrosis. It is controversial whether the underlying systemic inflammation of psoriasis is contributing to development of NAFLD or if comorbid diseases such as obesity enhance NAFLD development. Recent findings indicate that cytokine-mediated inflammation through TNFα, interleukin (IL)-6 and IL-17 might be the common link between psoriasis and NAFLD. Considering the shared inflammatory pathways, IL-17 pharmacological blockade, which is already well-established for psoriasis, may be a promising strategy to treat both psoriasis and NAFLD. Therefore, early detection of NAFLD and a better understanding of its pathophysiology in the context of the systemic inflammation in psoriasis is important with regard to individualized treatment approaches.},
  language  = {en}
}
@article{IckrathStoevesandtSchulmeyeretal.2021,
  author    = {Ickrath, Franziska and Stoevesandt, Johanna and Schulmeyer, Lena and Glatzel, Caroline and Goebeler, Matthias and Kerstan, Andreas},
  title     = {Metastatic Crohn's disease: an underestimated entity},
  series = {Journal of the German Society of Dermatology},
  volume    = {19},
  journal   = {Journal of the German Society of Dermatology},
  number    = {7},
  doi       = {10.1111/ddg.14447},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258435},
  pages     = {973-982},
  year      = {2021},
  abstract  = {Cutaneous metastatic Crohn's disease (MCD) is a rare but challenging dermatologic manifestation of Crohn's disease. It is histologically defined as the presence of non-caseating granulomas at skin sites separated from and non-contiguous to the gastrointestinal tract. Cutaneous metastatic Crohn's disease should be distinguished from the much more frequent contiguous cutaneous manifestations of Crohn's disease that present at perianal or, less common, peristomal sites with direct extension from the intestine to the adjacent skin. Versatile clinical presentation and the fact that occurrence can predate the initial diagnosis of Crohn's disease may lead to misdiagnosis, delayed treatment and underreporting. As case numbers are small and randomized controlled studies on management are lacking, the therapeutic approach remains challenging and is often unsatisfactory. We here performed a systematic literature search identifying 264 published pediatric and adult cases of MCD and additionally report three of our own cases. Our review summarizes clinical characteristics, putative etiopathology, histologic findings, differential diagnoses and treatment options for MCD.},
  language  = {en}
}
@article{GlutschKneitzGesierichetal.2021,
  author    = {Glutsch, Valerie and Kneitz, Hermann and Gesierich, Anja and Goebeler, Matthias and Haferkamp, Sebastian and Becker, J{\"u}rgen C. and Ugurel, Selma and Schilling, Bastian},
  title     = {Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma},
  series = {Cancer Immunology, Immunotherapy},
  volume    = {70},
  journal   = {Cancer Immunology, Immunotherapy},
  number    = {7},
  issn      = {14320851},
  doi       = {10.1007/s00262-020-02832-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265635},
  pages     = {2087-2093},
  year      = {2021},
  abstract  = {Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking. Methods At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated. Results Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy. Conclusion In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.},
  language  = {en}
}
@article{StolzeTrautmannGoebeleretal.2016,
  author    = {Stolze, Ina and Trautmann, Axel and Goebeler, Matthias and Stoevesandt, Johanna},
  title     = {Dangerous Leg Cramps: Severe Pustular Exanthema Caused by an Over-the-Counter Drug},
  series = {Acta Dermato-Venereologica},
  volume    = {96},
  journal   = {Acta Dermato-Venereologica},
  doi       = {10.2340/00015555-2324},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171285},
  pages     = {703-704},
  year      = {2016},
  abstract  = {Abstract is missing},
  language  = {en}
}
@article{SchmidtSticherlingSardyetal.2020,
  author    = {Schmidt, Enno and Sticherling, Michael and S{\´a}rdy, Mikl{\´o}s and Eming, R{\"u}diger and Goebeler, Matthias and Hertl, Michael and Hofmann, Silke C. and Hunzelmann, Nicolas and Kern, Johannes S. and Kramer, Harald and Nast, Alexander and Orzechowski, Hans-Dieter and Pfeiffer, Christiane and Schuster, Volker and Sitaru, Cassian and Zidane, Miriam and Zillikens, Detlef and Worm, Margitta},
  title     = {S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update},
  series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {18},
  journal   = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {5},
  doi       = {10.1111/ddg.14097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217806},
  pages     = {516 -- 526},
  year      = {2020},
  language  = {en}
}