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Startseite > Forschung > Arbeitsgruppen > Arbeitsgruppe Prof. Dr. med. Dieter Kabelitz > english version Kabelitz

 Research Group Prof. Dr. med. Dieter Kabelitz

 Kabelitz_Dieter

 

 

1. Name of group

 Senior Group Kabelitz

 

2. Key sentence

γδ T cells can kill a broad range of tumor cells and have great potential for immunotherapy. Our research aims at optimizing the effector functions of human γδ T cells to improve their clinical application.

 

3. Keywords

γδ T cells, immunotherapy, Vitamin C, pattern recognition receptors, TGF-β

 

4. Group members

  • Group leader: Prof. Dr. med. Dieter Kabelitz
  • Scientist: Dr. rer. nat. Christian Peters
  • Technician: Monika Kunz
  • PhD students: Léonce Kouakanou, Rubén Serrano
  • Medical students: Julia Feder, Tim Schricker
  • Guest: Nathalie Kidd (Fulbright fellowship)

 

5. Scientific Profile

 

γδ T cells account for 2-5% of peripheral blood T cells. The majority of blood-derived γδ T cells expresses a T-cell receptor of paired Vγ9 and Vδ2 chains. Rather than peptides presented by MHC/HLA molecules, Vγ9Vδ2 T cells recognize small phosphorylated molecules (“phosphoantigens”) derived from microbes or overproduced by tumor cells. The transmembrane butyrophilin protein family member BTN3A1 plays an indispensable role in this process. γδ T cells have recently attracted great attention as possible effector cells in tumor immunotherapy because they can kill different tumor cells without HLA restriction. Our overall interest is to shed light on the plasticity of human γδ T-cell and thereby to optimize the efficacy of γδ T cell functions.

Previously, we have extensively characterized the activation requirements, effector functions and tumor reactivity of human γδ T cells and we have performed in-depth immunophenotyping in cancer patients (e.g., glioblastoma). In on-going projects, we investigate (1) the modulation of the functional plasticity and effector functions of γδ T cells by epigenetic modifiers, cytokines, and co-stimulatory pathways, as well as (2) the effect of ligands for innate immune sensors on the interplay between γδ T cells and tumor cells.

 

List of scientific projects

  • Modulation of human γδ T cell activation and effector functions by Vitamin C
  • Modulation of the interaction between γδ T cells and tumor cells by TLR7/8 and STING ligands
  • Regulatory functions of human γδ T cells
  • Impact of TGF-β on γδ T cell differentiation

 

6.   Selected publications

  1. G. Chitadze, H.H. Oberg, D. Wesch, D. Kabelitz. The ambiguous role of γδ T lymphocytes in anti-tumor immunity. Trends Immunol 38: 668-678 (2017)
  2. C. Peters, R. Häsler, D. Wesch, D. Kabelitz. Human Vδ2 T cells are a major source of interleukin-9. Proc Natl Acad Sci USA 113, 12520-12525 (2016)
  3. Nerdal PT, Peters C, Oberg HH, Zlatev H, Lettau M, Quabius ES, Sousa S, Gonnermann D, Auriola S, Olive D, Määttä J, Janssen O, Kabelitz D. Butyrophilin 3A/CD277-dependent activation of human γδ T Cells: accessory cell capacity of distinct leukocyte populations. J Immunol. 197:3059-3068 (2016)
  4. E.P. Dopfer, F.A. Hartl, H.H. Oberg, G.M. Siegers, O.S. Yousefi, S. Kock, G.J. Fiala, B. Garcillán, A. Sandstrom, B. Alarcón, J.R. Regueiro, D. Kabelitz, E.J. Adams, S. Minguet, D. Wesch, P. Fisch, W.W.A. Schamel. The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing.  Cell Rep 7, 1704-1715 (2014)
  5. D. Kabelitz, A. Bender, T. Prospero, S. Wesselborg, O. Janssen, K. Pechhold. The primary response of human γδ-positive T cells to mycobacterium tuberculosis is restricted to Vγ9-expressing cells. J Exp Med 173:1331-1338 (1991)

 

Complete Publication list

http://www.researcherid.com/rid/A-2757-2010

https://www.ncbi.nlm.nih.gov/pubmed/?term=kabelitz+d

 

7.   Third party funding

  • DFG Ka 502/19-1 “Plasticity of human γδ T cells: (Epigenetic) modulation by Vitamin C”
  • DFG KA 502/16-1 “Regulation of human γδ T cell activation by neutrophils”
  • DFG ExC306 Cluster Laboratory VII
  • DFG Sino-German Cooperation Group Tumor Immunology
  • Wilhelm Sander-Stiftung project 2018.045.1: “Modulation of the interaction between γδ T cells and tumor cells by TLR7/8 and STING ligands”
  • Roggenbruck Stiftung (C. Peters) “Immunotherapy of solid tumors with TGFβ-expanded human Vδ2 γδ T cells”
  • DAAD long-term fellowships: L. Kouakanou, R. Serrano

 

8.   List of cooperation partners in alphabetical order

  • Dr. Jaydeep Bhat, MPI for Molecular Genetics, Berlin, Germany
  • Dr. Christoph Coch, University of Bonn, Clinical Chemistry, Bonn, Germany
  • Dr. Daniela Esser, University of Kiel, Institute for Experimental Medicine, Kiel, Germany
  • Prof. Gunther Hartmann, University of Bonn, Clinical Chemistry, Bonn, Germany
  • Prof. Adrian Hayday, King’s College London, London, United Kingdom
  • Prof. Christoph Kaleta, University of Kiel, Institute of Experimental Medicine, Kiel, Germany
  • Prof. Jorma Määttä, Dept of Cell Biology, Turku University, Turku, Finland
  • Prof. Daniel Olive, INSERM U 1068, Marseille, France
  • Prof. Martin Vingron, MPI for Molecular Genetics, Berlin, Germany
  • Prof. Zhigang Yin, Jinan University, Biomedical Center, Guangzhou, China