Tumour Microenvironment and Immunity

Tumour formation and tumour progression is the result of a coupling of cancer cells with different cell types from the tumour microenvironment and  their interaction with the surrounding extra-cellular matrix. The survival advantage of cancerous cells results from a symbiotic interaction  of cancer cells with their neighbouring cells. Furthermore, as a consequence of the dysregulation of the signal cascades in cancer cells these cells survive and there is a release of factors which actively modulate the microenvironment. Target cells for factors produced in the tumour: (i.)  endothelial cells, fibroblasts and fibroblast-similar strumal cells which synthesise the specific extra-cellular matrix proteins and (ii.) immune system cells. The erection of a barrier against penetrating immune cells and changes in the cellular immunity determine the microenvironment of the tumour and the grade of the tumour immunogenicity. In order to build metastases elsewhere, additional changes to the cancer cells are necessary, e.g. the activation of proteases and specific adhesion molecules. Research in this field leads to the development of new therapeutic strategies which, through focusing on specific components of the tumour microenvironment, can reduce tumour growth. Working  groups in Köln and Bonn that are active in this area, focus on a number of essential aspects of microenvironment and immunity.

Collaborative Research Centers

• CRC 670
  Cell-autonomous Immunity
• CRC 829
  Molecular Mechanisms regulating Skin Homeostasis
• CRC 832
  Molecular Basis and Modulation of Cellular Interactions in the Tumour Microenvironment

Molecular Mechanisms of Tumour Development

Professor Michael Hallek, Associate Professor Günter Fingerle-Rowson and Dr Günter Krause investigate Src kinases in the regulation of Leukemogenesis. The working proups of Professor Manolis Pasparakis, Associate Professor Francisco Rivero-Crespo and Dr Catherin Niemann research the role of RhoBTBs, NF-kB and MAPK as well as the Catenin-signals in the development of cancer. Professor  Nicolas Wernert examines Ets transcription factors in neoplastic cells  and tumour stroma during angiogenesis and invasion. Professor Martin Krönke is deals with  sphingomyelinase in the development of skin cancer. Professor Andreas Zimmer describes the signal pathways of  cannabinoid receptors which lead to cell proliferation and apoptosis. Associate Professor Hamid Kashkar and Professor Agapios Sachinidis analyse the mechanisms which inhibit cancer cell apoptosis and induce genes which send the cells survival signals.

Viruses and Cancer

Professor Ulrich Spengler researches the effect of TLR2-mediated recognition of hepatitis C (HCV)-components  of the anti-tumour immunity and the consequence for tumour spread. Two additional projects concentrate on the human papilloma virus (HPV): Professor Ulrike Wieland investigates the role of HPV in the tumour genesis in  anogenital and cutaneous skin cancer.

Stem Cells and Tumour Stem Cells

The research groups of Professor Jürgen Hescheler and Professor Oliver Brüstle conduct  a comparative analysis of human brain stem cells and the population of human embryonic stem cells to identify key events in the transition of stem cells to tumour stem cells. Professor Bernd K. Fleischmann works on the plasticity differentiation and tumor genesis of adult stem cells.

Microenvironment and Migration

The working groups around Professors Thomas Krieg, Monique Aumailley, Cornelia Mauch, Mats Paulsson and Manuel Koch have particular experience in the area of interaction between the cell and extra-cellular matrix, in the description of new matrix components, proteolytic enzymes and their role in cell migration and tumour invasion. These groups are working closely with Professor Carien Niessen, who investigates the effects of epithelial cancer caused by changes in the inter-cellular adhesion and polarity. Professor Waldemar Kolanus discovered the signal molecule  CYTIP which interacts closely with the integrin-binding protein Cytohesin-1. He researched the intra-cellular mechanisms of cell adhesion and its effect on cell migration and invasion, T-cell activation and the maturation of dendritic cells. Associate Professor Volker Schmitz investigates the effect of the inflammation cascade  in liver metastises; his goal is the identification of factors responsible for the distribution and spread of cancerous liver cells.

Immune Tolerance

Presently, a total of seven working groups is involved in decoding the role of immune tolerance in tumour progression. Professor Percy Knolle investigates the tolerance induction through antigen-presenting liver cells and specific molecular mechanisms to interrupt the tolerance induction. Andreas Limmer researches tolerance induction mechanisms in the liver and the spleen and develops new methods for the decimation of regulatory T-cells. Associate Professor Axel Roers determines the specific role of IL-10 from various cellular origins in the regulation of spontaneous anti-tumour immune reactions in vivo. Associate Professor Jens Chemnitz identifies signal pathways of the co-inhibitory receptors PD-1, CTLA-4 and BTLA on CD4+ T-cells and describes the role of different mechanisms which lead to the  inhibition of CD4+ T-cells in tumours of patients with Hodgkin-sarcoma. Dr Marc Beyer and Professor Joachim Schultze have identified new regulatory T-cell specific markers using genomic methods. Associate Professor Tjoung-Won Park researches the inhibition of  congenital immunity in ovarian cancer.

Immune Activation

Dr Winfried Barschet researches the immune system’s recognition of viral and nucleic acids  through cytosolic helicasesand has developed synthetic oligonucleotide ligands for cancer immune therapy.  Professor Gunther Hartmann studies TLR-Expression profiles and activation through corresponding ligands in the leukaemia cells.  Professor Christian Kurts’ goal is to increase immunity to tumours by improving the presentation of tumour-antigens in the dendritic cells.  He has developed innovative techniques specifically focused on the interaction of tumour-antigens with dendritic cells.  Professor Elke Pogge-von Strandmann is working on the interaction of receptor ligands in tumours, which modulate the activation of NK-cells.

Tumour - Animal Model

Professor Thomas Tüting has developed a new transgenic mouse model for the spontaneous  formation of melanoma. He investigates the biological role of Type I interferon (Typ I Inf) in tumour formation and progression. Dr Ines Gütgemann has developed a novel inducible orthotopic mouse model of the hepato-cellular carcinoma. Professor Herbert Pfister established the first transgenic mouse model to research the cancer development by human papillary virus (HPV). Professor Hubert Schorle provides animal models for the investigation of molecular mechanisms of tumour genesis and progression, and the detection of relevant signal transduction pathways in the creation of expression profiles.

Research Teams for Tumour Microenvironment and Immunity