ZMB Member Annette Paschen

ZMB Member
Annette Paschen

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Annette Paschen portrait
© UKE/Paschen

Prof. Dr. Annette Paschen

Clinic for Dermatology
University Hospital Essen
Hufelandstraße 55
45147 Essen

Research Overview

Treatment of advanced metastatic melanoma has for decades been a story of limited clinical success. This dramatically changed with the recent clinical implementation of two types of therapies: immunotherapy based on immunomodulating antibodies, termed immune checkpoint blocking therapy (ICBT), and targeted therapies employing inhibitors of the oncogenic MAPK signaling pathway. Those treatments can induce remarkable clinical responses in a subgroup of patients, but still the majority of patients is resistant to therapy or develops resistance after initial therapy response. There is accumulating evidence for a fundamental role of adaptive and innate cytotoxic lymphocytes, tumor antigen-specific T cells and natural killer (NK) cells, respectively, in tumor cell elimination not only in the course of immunotherapy but also targeted therapy. Both, adaptive and innate lymphocytes can recognize melanoma cells as “abnormal self” but by different mechanisms. Within the research group “Molecular Tumor Immunology” we study the interaction of melanoma cells with tumor antigen-specific CD4+ / CD8+ T cells and NK cells. In particular we focus on resistance mechanisms allowing tumor cells to escape either from recognition or killing by T cells and NK cells (immune escape). Our own studies suggest that melanoma immune escape sets a barrier to successful ICBT and targeted therapy indicating the need to unravel the underlying molecular resistance mechanisms for improvement of treatment regimens.
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Selected Publications

    Journal articles

  • Chauvistré, Heike; Shannan, Batool; Daignault-Mill, Sheena M.; Ju, Robert J.; Picard, Daniel; Egetemaier, Stefanie; Váraljai, Renáta; Gibhardt, Christine S.; Sechi, Antonio; Kaschani, Farnusch; Keminer, Oliver; Stehbens, Samantha J.; Liu, Qin; Yin, Xiangfan; Jeyakumar, Kirujan; Vogel, Felix C. E.; Krepler, Clemens; Rebecca, Vito W.; Kubat, Linda; Lueong, Smiths S.; Forster, Jan; Horn, Susanne; Remke, Marc; Ehrmann, Michael; Paschen, Annette; Becker, Jürgen; Helfrich, Iris; Rauh, Daniel; Kaiser, Markus; Gul, Sheraz; Herlyn, Meenhard; Bogeski, Ivan; Rodríguez-López, José Neptuno; Haass, Nikolas K.; Schadendorf, Dirk; Rösch, Alexander
    Persister state-directed transitioning and vulnerability in melanoma
    In: Nature Communications Vol. 13 (2022) Nr. 1, 3055
  • Cheung, Phyllis F.; Yang, JiaJin; Fang, Rui; Borgers, Arianna; Krengel, Kirsten; Stoffel, Anne; Althoff, Kristina; Yip, Chi Wai; Siu, Elaine H. L.; Ng, Linda W. C.; Lang, Karl S.; Cham, Lamin B.; Engel, Daniel Robert; Soun, Camille; Cima, Igor; Scheffler, Björn; Striefler, Jana K.; Sinn, Marianne; Bahra, Marcus; Pelzer, Uwe; Oettle, Helmut; Markus, Peter; Smeets, Esther M. M.; Aarntzen, Erik H. J. G.; Savvatakis, Konstantinos; Liffers, Sven-Thorsten; Lueong, Smiths S.; Neander, Christian; Bazarna, Anna; Zhang, Xin; Paschen, Annette; Crawford, Howard C.; Chan, Anthony W. H.; Cheung, Siu Tim; Siveke, Jens
    Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression
    In: Nature Communications Vol. 13 (2022) Nr. 1, 156
  • Pieper, Natalia; Zaremba, Anne; Leonardelli, Sonia; Harbers, Franziska Noelle; Schwamborn, Marion; Lübcke, Silke; Schrörs, Barbara; Baingo, Jolanthe; Schramm, Alexander; Haferkamp, Sebastian; Seifert, Ulrike; Sucker, Antje; Lennerz, Volker; Wölfel, Thomas; Schadendorf, Dirk; Schilling, Bastian; Paschen, Annette; Zhao, Fang
    Evolution of melanoma cross-resistance to CD8⁺ T cells and MAPK inhibition in the course of BRAFi treatment
    In: OncoImmunology Vol. 7 (2018) Nr. 8, e1450127
  • López-Cobo, Sheila; Pieper, Natalia; Campos-Silva, Carmen; García-Cuesta, Eva M.; Reyburn, Hugh T.; Paschen, Annette; Valés-Gómez, Mar
    Impaired NK cell recognition of vemurafenib-treated melanoma cells is overcome by simultaneous application of histone deacetylase inhibitors
    In: OncoImmunology Vol. 7 (2018) Nr. 2, e1392426
  • Sucker, Antje; Zhao, Fang; Pieper, Natalia; Heeke, Christina; Maltaner, Raffaela; Stadtler, Nadine; Real, Birgit; Bielefeld, Nicola; Howe, Sebastian; Weide, Benjamin; Gutzmer, Ralf; Utikal, Jochen; Loquai, Carmen; Gogas, Helen; Klein-Hitpaß, Ludger; Zeschnigk, Michael; Westendorf, Astrid; Trilling, Mirko; Horn, Susanne; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus; Paschen, Annette
    Acquired IFNγ 3 resistance impairs anti-Tumor immunity and gives rise to T-cell-resistant melanoma lesions
    In: Nature Communications Vol. 8 (2017) 15440
  • Sucker, Antje; Paschen, Annette
    Deciphering the genetic evolution of T-cell resistance in melanoma
    In: OncoImmunology Vol. 4 (2015) Nr. 5, e1005510
  • Schilling, Bastian; Paschen, Annette
    Immunological consequences of selective BRAF inhibitors in malignant melanoma : Neutralization of myeloid-derived suppressor cells
    In: OncoImmunology Vol. 2 (2013) Nr. 8, e25218
  • Heinemann, Anja; Paschen, Annette
    Tumor suppressors control ULBP2, an innate surface ligand of the lymphocyte immune receptor NKG2D
    In: OncoImmunology Vol. 1 (2012) Nr. 4, pp. 535 - 536