Overview

FOUNDED IN 2007, THIS YEAR WE ARE CELEBRATING A DECADE OF EXPERIMENTAL AND TRANSLATIONAL RESEARCH IN ESSEN

Welcome to the Research Division of the Department of Otorhinolaryngology at the University Hospital Essen, part of the West German Cancer Center.

Founded in 2007 we have since become a leading place for experimental research in head and neck oncology as well as cell biology not only in Germany but world-wide. We have a special interest in the immunological tumor-host interaction with a particular focus on neutrophils and myeloid-derived suppressor cells. A second research theme of the division aims at better understanding the immunoregulatory properties of so-called mesenchymal stromal cells. In the last ten years we have authored or co-authored over 80 peer-reviewed publications, some of which are highly cited. Please find below a brief overview of our research activities and publications. More detailed information is provided by clicking on the additional web-links.

With kind regards

Sven Brandau, PhD

Head of the Research Division

Over the last ten years we have established and worked on the following three main research themes:

In spite of the potential recognition of malignant cells by the immune system and a resulting anti-tumor immune response, this reaction is mostly insufficient and subclinical. This is mainly caused by tumour-induced immune regulatory and immune suppressive mechanisms. In the last years, a variety of these mechanisms have been identified. Head and neck cancer (HNC) is also characterized by a particular immunosuppressive cancer-related inflammation. Thus, a better understanding of the reciprocal interaction of tumour tissue and host immunity forms the basis for identification of new therapeutic possibilities for intervention in HNC and other tumor entities.

 

Over the last years the group has provided substantial insight into the role of neutrophils and myeloid-derived suppressor cells (MDSC) in tumor host interaction. We have identified mechanisms and pathways involved in the modulation of neutrophils and MDSC. We have also elucidated mechanisms used by those cells to promote tumor progression. Lastly, we have determined the prognostic relevance of selected cellular and molecular components of the tumor-immune-interplay for disease outcome in patients with head and neck cancer.

More recently, Dr. Jadwiga Jablonska joined the Division and is now leading the research group “translational oncology”. Over the last years, using genetic mouse models, Dr. Jablonska has especially focused on the role of interferons in modulation of tumor-associated neutrophils.  Based on her work, interfering with the function of tumor-promoting neutrophils may thus provide another means to therapeutically shape the tumor microenvironment.

 

Key publications:

Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, Lang S. (2011) Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol. 89(2), 311-317

Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. (2010) Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 120(4):1151-64.

Dumitru CA, Gholaman H, Trellakis S, Bruderek K, Dominas N, Gu X, Bankfalvi A, Whiteside TL, Lang S, Brandau S. (2011) Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer. 129(4), 859-869

Davey MS, Tamassia N, Rossato M, Bazzoni F, Calzetti F, Bruderek K, Sironi M, Zimmer L, Bottazzi B, Mantovani A, Brandau S, Moser B, Eberl M, Cassatella MA. (2011) Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol. (correspondence) 12(11):1017-8.

Klein JC, Moses K, Zelinskyy G, Sody S, Buer J, Lang S, Helfrich I, Dittmer U, Kirschning CJ, Brandau S. Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth. (2017) Nat Commun. 8:14600.

Even in the absence of classical tumor antigens, tumors harbor molecular structures, which can be used as targets for immunological or biological therapy. We are researching the effects of therapeutic antibodies directed against established (such as EGFR) or newly identified (collaboration R. Zeidler, Munich) target proteins on cancer cells. These antibodies may either directly inhibit the target protein or induce activation of immune cells. In addition we exploit the use of immunostimulatory toll-like receptor agonists to either stimulate immunity or induce cell death in tumor cells. Finally we are looking into differences of HPV+ versus HPV- HNC as well as the potential of HPV to serve as a target for immunological cancer therapy.

 

Key publications:

Klein JC, Wild CA, Lang S, Brandau S. (2016) Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands. Cancer Immunol Immunother. 65(6): 689-700

Busche A, Goldmann T, Naumann U, Steinle A, Brandau S. (2006) NK-mediated rejection of experimental human lung cancer by genetic overexpression of MICA. Hum Gene Ther 17 (2), 135-146

 

Kalkavan H, Sharma P, Kasper S, Helfrich I, Pandyra AA, Gassa A, Virchow I, Flatz L, Brandenburg T, Namineni S, Heikenwalder M, Höchst B, Knolle PA, Wollmann G, von Laer D, Drexler I, Rathbun J, Cannon PM, Scheu S, Bauer J, Chauhan J, Häussinger D, Willimsky G, Löhning M, Schadendorf D, Brandau S*, Schuler M*, Lang PA*, Lang KS*. (2017) Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression. Nat Commun. 8:14447. * co-senior authors

Vahle AK, Kerem A, Oztürk E, Bankfalvi A, Lang S, Brandau S. (2012) Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice – role of toll-like-receptor 4 expressed on host cells. Cancer Lett. 317(2), 199-206

Mesenchymal stromal cells (MSCs) are fibroblastoid progenitor cells with multi-lineage differentiation potential. Next to their tissue regenerative properties, MSC also display strong immunoregulatory potential. We are interested in understanding the immunobiology of MSCs from the bone-marrow and from different tissues of the head and neck region. In particular, we are investigating their interaction with innate and adaptive immune cells, their response to immunological stimulation as well as their role in the tumor microenvironment.

 

Key publications:

Dumitru CA, Hemeda H, Jakob M, Lang S, Brandau S. (2014) Stimulation of mesenchymal stromal cells (MSCs) via TLR3 reveals a novel mechanism of autocrine priming. FASEB J. 28(9):3856-66

Kansy BA, Dißmann PA, Hemeda H, Bruderek K, Westerkamp AM, Jagalski V, Schuler P, Kansy K, Lang S, Dumitru CA, Brandau S. (2014) The bidirectional tumor – mesenchymal stromal cell interaction promotes the progression of head and neck cancer. Stem Cell Res Ther. 5(4):95.

Brandau S, Jakob M, Hemeda H, Bruderek K, Janeschik S, Bootz F, Lang S. (2010) Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge. J Leukoc Biol. 88(5), 1005-15

Hemeda H, Jakob M, Ludwig A, Giebel B, Lang S, Brandau S. (2010) Interferon-gamma and Tumor Necrosis Factor-alpha Differentially Affect Cytokine Expression and Migration Properties of Mesenchymal Stem Cells. Stem Cells Dev 19(5), 693-706

To accomplish the tasks mentioned above we are using a broad spectrum of methods branching from molecular and cellular immunology to murine models all the way to the analysis of patient material.