Decades of basic and tumor immunology research have identified key factors hampering proper anti-tumor immune response, including suppressive T cells, Inhibitory checkpoint molecules, and suppressive cytokines secreted by tumor- and antigen-presenting cells. Such discoveries have led to the development of many novel treatments that revolutionized  cancer therapy.

While tumor immunology research is currently focused on the study of inhibitory surface markers, such as PD-1, CTLA-4, TIGIT, and TIM3, we search in the deep sea where epigenetic factors shove the first immune dysfunction signal in cancer patients. The search for transcriptional factors that initiate T cell exhaustion program, in cancer patients, will help us identify intracellular novel drug targets that should shape the next generation cancer immunotherapy.

As a part of the largest study group focusing on Multiple Myeloma in Germany, the German-speaking Myeloma Multicenter Group “GMMG”, we utilize the combination of clinical outcomes gathered through our clinical trial with high throughput genomics approaches, as well as T cell functional assays, to investigate the transcriptional pathways that are involved in tumor escape mechanisms.

In our previous work, we examined the predictive and prognostic values of immunological markers expression in patients with Multiple Myeloma and identified the role of transcriptional factors expression in T cells.

Our Laboratory approaches include Flow Cytometry, RT-PCR, Western Blotting, CRISPR Cas9 Knock out, RNA bulk Seq, Single Cell Seq, Luciferase Reporter Assay, ELISA, and ELISPOT. 

Our current projects:

1. The Immunomodulatory Impact of IKZFs expression on T cells in patients with Multiple Myeloma.
2. Immuno-reconstitution analyses of patients enrolled in the GMMG-HD7 clinical trial.
3. The Identification of transcriptional factors that guide CD8+ cells towards exhaustion state in cancer patients.

Meet our team

Collaborators

German-speaking Myeloma Multicenter Group (GMMG)

Laboratory for Hematological Diagnostics and Biobanking in University Hospital Heidelberg

The Johns Hopkins University School of Medicine in USA (Ivan Borrello)

Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Hakim Echchannaoui)

Division of Biostatistics in the German Cancer Research Center DKFZ (Axel Benner)

Division of Applied Bioinformatics in the German Cancer Research Center DKFZ (Benedikt Brors)

Universitätsklinikums Erlangen (AG Bruns)

EMBL (Genomics and Proteomics Core Facilities)

University of Navarra (Bruno Paiva)

The Multiple Myeloma Research Foundation in USA (MMRF)

Selected Publication

Katharina Kriegsmann, Gigi Nu Hoang Quy Ton, Mohamed H. S. Awwad, Axel Benner, Uta Bertsch, Britta Besemer, Mathias Hänel, Roland Fenk, Markus Munder, Jan Dürig, Igor W. Blau, Stefanie Huhn, Dirk Hose, Anna Jauch, Christoph Mann, Niels Weinhold, Christof Scheid, Roland Schroers, Ivana von Metzler, Aneta Schieferdecker, Jörg Thomalla, Peter Reimer, Rolf Mahlberg, Ullrich Graeven, Stephan Kremers, Uwe M. Martens, Christian Kunz, Manfred Hensel, Andrea Seidel-Glätzer, Katja C. Weisel, Hans J. Salwender, Carsten Müller-Tidow, Marc S. Raab, Hartmut Goldschmidt, Elias K. Mai & Michael Hundemer
CD8+ CD28− regulatory T cells after induction therapy predict progression-free survival in myeloma patients: results from the GMMG-HD6 multicenter phase III study, Leukemia (2024)
Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy, Nature Communications 2024

Raphael Lutz, Florian Grünschläger, Malte Simon, Mohamed H. S. Awwad, Marcus Bauer, Schayan Yousefian, Niklas Beumer, Lea Jopp-Saile, Anastasia Sedlmeier, Llorenç Solé-Boldo, Bogdan Avanesyan, Dominik Vonficht, Patrick Stelmach, Georg Steinbuss, Tobias Boch, Simon Steiger, Marc-Andrea Baertsch, Nina Prokoph, Karsten Rippe, Brian G. M. Durie, Claudia Wickenhauser, Andreas Trumpp, Carsten Müller-Tidow, Daniel Hübschmann, Niels Weinhold, Marc S. Raab, Benedikt Brors, Hartmut Goldschmidt, Charles D. Imbusch, Michael Hundemer* & Simon Haas*

Mohamed H. S. Awwad, Abdelrahman Mahmoud, Heiko Bruns, Hakim Echchannaoui, Katharina Kriegsmann, Raphael Lutz, Marc S. Raab, Uta Bertsch, Markus Munder, Anna Jauch, Katja Weisel, Bettina Maier, Niels Weinhold, Hans Jürgen Salwender, Volker Eckstein, Mathias Hänel, Roland Fenk, Jan Dürig, Benedikt Brors, Axel Benner, Carsten Müller-Tidow, Hartmut Goldschmidt & Michael Hundemer, Selective elimination of immunosuppressive T cells in patients with multiple myeloma, Leukemia (2021)

K. Kriegsmann, M.-A. Baertsch, M.H.S. Awwad, M. Merz, D. Hose, A. Seckinger, A. Jauch, N. Becker, A. Benner, M.S. Raab, J. Hillengass, U. Bertsch, J. Dürig, H.J. Salwender, M. Hänel, R. Fenk, M. Munder, K. Weisel, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients, Blood Cancer J. 9 (2019)

K. Kriegsmann, M. Kriegsmann, M. Cremer, M. Schmitt, P. Dreger, H. Goldschmidt, C. Müller-Tidow, M. Hundemer, Cell-based immunotherapy approaches for multiple myeloma, Br. J. Cancer 120 (2019)

M.H.S. Awwad, K. Kriegsmann, J. Plaumann, M. Benn, J. Hillengass, M.S. Raab, U. Bertsch, M. Munder, K. Weisel, H.J. Salwender, M. Hänel, R. Fenk, J. Dürig, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma, Oncoimmunology 7 (2018)

J. Plaumann, M. Engelhardt, M.H.S. Awwad, H. Echchannaoui, E. Amman, M.S. Raab, J. Hillengass, N. Halama, B. Neuber, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, IL-10 inducible CD8+ regulatory T-cells are enriched in patients with multiple myeloma and impact the generation of antigen-specific T-cells, Cancer Immunol. Immunother. 67 (2018)

B. Neuber, J. Dai, W.A. Waraich, M.H.S. Awwad, M. Engelhardt, M. Schmitt, S. Medenhoff, M. Witzens-Harig, A.D. Ho, H. Goldschmidt, M. Hundemer, Lenalidomide overcomes the immunosuppression of regulatory CD8+CD28- T-cells, Oncotarget 8 (2017)

A.Seckinger, J.A. Delgado, S. Moser, L. Moreno, B. Neuber, A. Grab, S. Lipp, J. Merino, F. Prosper, M. Emde, C. Delon, M. Latzko, R. Gianotti, R. Lüoend, R. Murr, R.J. Hosse, L.J. Harnisch, M. Bacac, T. Fauti, C. Klein, A. Zabaleta, J. Hillengass, E.A. Cavalcanti-Adam, A.D. Ho, M. Hundemer, J.F. San Miguel, K. Strein, P. Umaña, D. Hose, B. Paiva, M.D. Vu, Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment, Cancer Cell 31 (2017)

 I. Krämer, M. Engelhardt, S. Fichtner, B. Neuber, S. Medenhoff, U. Bertsch, J. Hillengass, M.-S. Raab, D. Hose, A.D. Ho, H. Goldschmidt, M. Hundemer, Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro, Oncoimmunology 5 (2016)

 S. Fichtner, D. Hose, M. Engelhardt, T. Meißner, B. Neuber, F. Krasniqi, M. Raab, S. Schönland, A.D. Ho, H. Goldschmidt, M. Hundemer, Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma, Clin. Cancer Res. 21 (2015)

M. Munder, M. Engelhardt, D. Knies, S. Medenhoff, G. Wabnitz, C. Luckner-Minden, N. Feldmeyer, R.-H. Voss, P. Kropf, I. Müller, R. Conradi, Y. Samstag, M. Theobald, A.D. Ho, H. Goldschmidt, M. Hundemer, Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion, PLoS ONE 8 (2013)