Research Group Prof. Dr. rer. nat. Daniela Wesch
1. Name of group
Cellular Tumor Immunology
2. Key sentence
The research group is interested in the characterization of cytotoxic- and regulatory properties of γδ T lymphocytes and their role in tumor immunology with a focus on ductal pancreatic adenocarcinomas (PDAC) and ovarian carcinomas.
γδ T lymphocytes, cytotoxicity, ovarian carcinoma, ductal pancreatic adenocarcinoma, immunotherapy, bispecific antibodies, tumor escape-mechanisms, flow cytometry
4. Group members
- Group leader: Prof. Dr. rer. nat. Daniela Wesch
- Scientist: PD Dr. sc. hum. Hans-Heinrich Oberg
- Physician: Lisa Janitschke (M.D. thesis)
- Students: Rubén D. Serrano Guerrero (Ph.D.), Vjola Sulaj (cand. med.), Annika Meyer (cand. med.)
5. Scientific profile
Cytotoxic γδ T lymphocytes are an attractive subpopulation of T lymphocytes, which offer certain advantages for novel strategies of T cell-based immunotherapy due to their plasticity in bridging innate and adaptive immunity. Cytotoxic lymphocytes can infiltrate into lymphomas and numerous epithelial tumors. Several γδ T lymphocytes recognize phosphorylated intermediates of the endogenous Mevalonate metabolic pathway in a HLA-independent manner. These intermediates often accumulate in tumor cells due to a dysregulation. The in vivo-relevance of human cytotoxic γδ T lymphocytes towards different tumour entities has already been demonstrated in various animal models as well as in clinical trials. Our recent studies in cooperation with Prof. M. Peipp (Dep. of Stem Cell- and Immunotherapy, UKSH) demonstrated that bispecific antibodies enhanced cytotoxicity designed of adoptively transferred γδ T lymphocytes against pancreatic tumors grafted into immunocompromized mice.
The activation of cytotoxic Tumor-infiltrating T lymphocytes can be negatively influenced by e.g. an immunosuppressive tumor environment, the accumulation of regulatory αβ- or γδ T lymphocytes in the tumor, different resistance mechanisms of the tumors or the induction of senescence/dormancy.
A substantial aim of our studies is to investigate the γδ TCR repertoire and the functional anti-tumor capacity of tumor-infiltrating γδ T lymphocytes of fresh tumor tissue in comparison to γδ T lymphocytes of autologous blood of pancreatic- or ovarian cancer patients. More insights into the molecular mechanisms of signaling pathways regulating cytotoxicity, proliferation and cytokine release of the different T cell subsets in the blood versus the tumor will help to improve the preparation of appropriate bispecific antibodies.
Additionally, we examine the different immunosuppressive mechanisms that prevent an effective immune response of tumor-infiltrating γδ T lymphocytes and possibilities to enhance cytotoxic activity of tumor-infiltrating γδ T lymphocytes by the usage of bispecific antibodies and / or Toll-like receptor agonists.
Our research projects in cooperation with our different collaborators should provide better insights in the role of γδ T lymphocytes in immune response and help to optimize immunotherapies.
List of the scientific projects
- γδ T cell activation, signaling and effector function in immunity, tolerance and oncology
- Characterization of different tumor escape mechanisms
- Cytometric Immunomonitoring
- Optimization of immunotherapies
6. Selected publications
- Oberg HH, Kellner C, Gonnermann D, Sebens S, Bauerschlag D, Gramatzki M, Kabelitz D, Peipp M, Wesch D (2018). Tribody [(HER2)2xCD16] is more effective than trastuzumab in enhancing γδ T cell and natural killer cell cytotoxicity against HER2-expressing cancer cells. Front Immunol 9:814.
- Gonnermann D, Oberg HH, Kellner C, Peipp M, Sebens S, Kabelitz D, Wesch D (2015). Cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells are resistant against γδ T cell cytotoxicity. OncoImmunol, 4: e988460.
- Oberg HH, Peipp M, Kellner C, Sebens S, Krause S, Petrick D, Adam-Klages S, Röcken C, Becker T, Vogel I, Weisner D, Freitag-Wolf S, Gramatzki M, Kabelitz D, Wesch D (2014). Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells. Cancer Res, 74: 1349-1360.
- Shojaei H, Oberg HH, Juricke M, Marischen L, Kunz M, Mundhenke C, Gieseler F, Kabelitz D, Wesch D (2009). Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human γδ T cells. Cancer Res 69:8710-8717.
- Wesch D, Beetz S, Oberg HH, Marget M, Krengel K, Kabelitz D (2006). Direct costimulatory effect of TLR3 ligand poly(I:C) on human γδ T lymphocytes. J Immunol 176:1348-1354.
Complete publication list
7. Third party funding
- DFG Research Unit FOR2799 (Receiving and Translating signals via the γδ T Cell Receptor), WE 3559/6-1: “Influence of bispecific antibodies on the interaction of T cells and tumor cells”
- Boehringer Ingelheim Vienna – sponsored Industry-cooperation-project investigating „γδ T-cell based immunotherapy approaches with novel designed immunoconstructs“
- Medizinische Fakultät (F357915): „TRAIL-Rezeptor 4 reguliert die T-Zellzytotoxizität in duktalen Pankreasadenokarzinom-Zellen“
8. List of cooperation partners in alphabetical order
- Prof. Dr. N. Arnold (Clinic for Gynecology and Obstetrics, UKSH, Kiel)
- Prof. Dr. D. Bauerschlag (Clinic for Gynecology and Obstetrics, UKSH, Kiel)
- Dr. C. Baumann / Dr. K.-P. Künkele (Boehringer Ingelheim, Vienna, Austria)
- PD Dr. A. Bergmann (Institute of Human Genetic, Medical University Hannover)
- Dr. C. Coch (Clinical Pharmacology, University of Bonn)
- Prof. Dr. M. Gramatzki (Dep. of Stem Cell- and Immunotherapy, UKSH, CAU Kiel)
- Prof. Dr. A. Hayday (The Francis Crick Institute, London, UK)
- Prof. Dr. T. Herrmann (Institute of Virology and Immunbiology, Würzburg)
- Prof. Dr. D. Kabelitz (Institute of Immunology, CAU, Kiel)
- PD Dr. C. Kellner (Medical University, LMU München)
- Prof. Dr. C. Mundhenke/ Dr. T. Schmidt (Clinic for Gynecology and Obstetrics, UKSH, Kiel)
- Prof. Dr. M. Peipp (Dep. of Stem Cell- and Immunotherapy, UKSH, CAU Kiel)
- Prof. Dr. I. Prinz (Institute of Immunology, Med. Hochschule Hannover)
- Dr. S. Ravens (Institute of Immunology, Med. Hochschule Hannover)
- Prof. Dr. C. Röcken (Institute of Pathology, UKSH, Kiel)
- Prof. Dr. W. Schamel (Institute of Biology III, Div. of Molecular Immunology, University of Freiburg)
- Prof. Dr. S. Sebens / PD Dr. C. Röder (Institute of Experimental Cancer Research, UKSH, CAU Kiel)
- Dr. G. Siegers (Dept. of Oncology, University of Alberta, Edmonton, Canada)
- Prof. Dr. A. Trauzold (Institute of Experimental Cancer Research, UKSH, CAU Kiel)
- Dr. J. Weimer (Clinic for Gynecology and Obstetrics, UKSH, Kiel)
- Dr. K. Wistuba-Hamprecht (Div. Of Dermatology, Medical Center University of Tübingen)