RG Macrophages (Bruns)

  • tumor-associated macrophages
  • antibody therapy
  • Multiple Myeloma

 

Scientific focus

Macrophages are the main component of the tumor microenvironment in the most malignancies. Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cytotoxicity, tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. However, TAMs are thought to be pro-tumorigenic because they promote angiogenesis and metastasis. The underlying mechanisms responsible for this observation remain unclear. Our research is focused on the functional and molecular analysis of the tumor microenvironment, and identifying and modulating potential therapeutic target structures. Our long-term goal is the specific targeting and modulating of the tumor microenvironment to enhance the effectiveness of immunotherapeutic strategies in malignant lymphomas.

 

Lab members

  • PD Dr. rer. nat. Heiko Bruns, principle investigator
  • Cindy Flamann, PhD student
  • Alexander Biedermann, PhD student
  • Katrin Bitterer, MTA
  • Magdalena Leffler, MTA
  • Heidi Balzer, MTA

 

Current projects

  1. Effector functions of TAMs in malignant lymphomas.
  2. Impact of immunmodulatory  drugs  on the tumor microenviroment.
  3. Transdifferentiation of malignant B-cells into macrophages.

 

Methods

  •  Flow cytometry
  • ELISA
  • Quantitative RT-PCR
  • Westernblot
  • Confocal microscopy
  • Chromatin immunoprecipitation
  • Isolation of  microvesicles by ultracentrifugation  
  • Untersuchung von TAMs in verschiedenen Mausmodellen

 

Collaborations intern

  • Christian Bach, Medizinische Klinik 5
  • Steffen Backert, Department Biologie
  • Jacobus Bosch, Medizinische Klinik 5
  • Maike Büttner, Pathologisches Institut
  • Udo Gaipl, Strahlenklinik
  • Markus Hoffmann, Medizinische Klinik 3
  • Dimitrios Mougiakakos, Medizinische Klinik 5

 

Collaborations extern

  • Fabian Beier, Medizinische Klinik IV, Universitätsklinikum RWTH Aachen
  • Mario Fabri, Klinik und Poliklinik für Dermatologie, Universitätsklinikum Köln
  • Thomas Graf, Centre for Genomic Regulation, Barcelona, Spanien
  • Jan Krönke,  Medizinische Klinik III, Universitätsklinikum Ulm 
  • Georg Lenz, Medizinische Klinik A, Universitätsklinikum Münster
  • Jens Nolting, Medizinische Klinik 3, Universitätsklinikum Bonn
  • Joachim L. Schultze, Life & Medical Sciences Institute (LIMES), Universität Bonn
  • Christian Schütz, Paul-Ehrlich-Institut, Langen
  • Steffen Stenger, Medizinische Mikrobiologie, Universitätsklinikum Ulm
  • Robert Zeiser, Klinik für Innere Medizin I, Hämatologie, Onkologie und Stammzelltransplantation Universitätsklinikum Freiburg

 

    Selected Publications

    Daniel Hofbauer, Dimitrios Mougiakakos, Luca Broggini, Mario Zaiss, Maike Büttner-Herold, Christian Bach, Bernd Spriewald, Frank Neumann, Savita Bisht, Jens Nolting, Robert Zeiser, Shaima’a Hamarsheh, Martin Eberhardt, Julio Vera, Cristina Visentin, Chiara Maria Giulia De Luca, Fabio Moda, Stefan Haskamp, Cindy Flamann, Martin Böttcher, Katrin Bitterer, Simon Völkl, Andreas Mackensen, Stefano Ricagno, and Heiko Bruns. (2021). β2-microglobulin - a trigger for NLRP3 inflammasome activation in tumor-associated macrophages promoting multiple myeloma progression.
    Immunity. 54(8):1772-1787.       

    The regulatory IKZF1-IRF4/IRF5 axis controls polarization of myeloma-associated macrophages. Dimitrios Mougiakakos, Christian Bach, Martin Böttcher, Fabian Beier, Linda Röhner, Andrej Stoll, Michael Rehli, Claudia Gebhard4, Christopher Lischer, Martin Eberhardt, Julio Vera, Maike Büttner-Herold, Katrin Bitterer, Heidi Balzer, Magdalena Leffler, Simon Jitschin, Michael Hundemer, Mohamed H. S. Awwad, Martin Busch, Steffen Stenger, Simon Voelkl, Christian Schütz, Jan Krönke, Andreas Mackensen, and Heiko Bruns.
    Cancer Immunol Res. 2021 Mar;9(3):265-278

    Bruns, H., Buttner, M., Fabri, M., Mougiakakos, D., Bittenbring, J. T., Hoffmann, M. H., Beier, F., Pasemann, S.,Jitschin, R., Hofmann, A. D., Neumann, F., Daniel, C., Maurberger, A., Kempkes, B., Amann, K., Mackensen, A. and Gerbitz, A., Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma. Sci. Transl. Med. (2015)

    Bruns, H., Bessell, C., Varela, J. C., Haupt, C., Fang, J., Pasemann, S., Mackensen, A., Oelke, M., Schneck, J. P. and Schutz, C., CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells. Clin. Cancer Res. (2015)

    Bruns H, Stegelmann F, Fabri M, Döhner K, van Zandbergen G, Wagner M, Skinner M,. Modlin RL and Stenger S. Abelson Tyrosine Kinase Controls Phagosomal Acidification Required for Killing of Mycobacterium tuberculosis in Human Macrophages. J Immunol. (2012)

    Fabri M., S. Stenger, D.-M. Shin, J.-M. Yuk, P. T. Liu, S. Realegeno, H.-M. Lee, S. R. Krutzik, M. Schenk, P. A. Sieling, R. Teles, D. Montoya, S. S. Iyer, Bruns H, D. M. Lewinsohn, B. W. Hollis,M. Hewison, J. S. Adams, A. Steinmeyer, U. Zügel, G. Cheng, E.-K. Jo, B. R. Bloom, R. L. Modlin. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. (2011)

    Bruns H, Meinken C, Schauenberg P, Härter G, Kern P, Modlin R, Antoni C, Stenger S. Anti-TNF immunotherapy reduces CD8+T cell mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J. Clin. Invest (2009)

     

    News release

    Mit-Vitamin-D-gegen-Krebs

    Vitamin-D-Hilfe-im-Kampf-gegen-Krebs (Interview im Deutschlandfunkt)

    Verwandlungskünstler im Fokus der Forschung

    PD Dr. Heiko Bruns (PI), D. Hofbauer (PhD student), M. Leffler (MTA), K. Bitterer (MTA), C. Flamann (PhD student), H. Balzer (MTA)