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

Effector functions of TAMs in malignant lymphomas.
Impact of immunmodulatory drugs on the tumor microenviroment.
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)