Cancer & Immunometabolism Research Group

Metabolism and immunology have been acknowledged as hallmarks of cancer, and it is now accepted that certain types of cancer are associated with metabolic disturbances such as obesity and obesity-associated chronic low-grade inflammation (so called metaflammation). Research in cancer immunometabolism can principally focus on three main aspects: First, cancer cell intrinsic changes of metabolism, e.g. a high glycolytic capacity, namely the Warburg effect, second, cancer cell extrinsic metabolic alterations that modulate cancer and immune cell biology, and third, the influence of immune cells on (systemic) metabolism.

We could recently show that Natural Killer (NK) cells, which are best known for their ability to directly kill infected or malignant cells, are critical mediators of metaflammation and glucose metabolism (Cell Metabolism 2017; Nat. Immunol. 2015). Using cutting-edge technologies such as multi-color flow cytometry and single cell sequencing, metabolomics, lipidomics and extracellular flux analysis in different mouse models, we are currently characterizing specific NK cell subpopulations with regard to their contribution to metaflammation and (obesity-associated) cancer biology.

The other focus of the lab is to understand immune responses within the tumor microenvironment and to develop strategies to therapeutically manipulate the tumor microenvironment, which could enhance cancer immunity. As an example, in close cooperation with the lab of Michael von Bergwelt-Baildon and Max Schlaak (Department of Dermatology, CIO Skin Cancer Center) we could recently show that tumor associated B-cells in cutaneous T cell lymphoma might be potential candidates for therapeutic interventions (JCO 2016).
Complemented by translational and clinical analyses as stated below the overall goal of our group is to develop innovative immunometabolic therapeutic strategies to fight cancer.

Specific aims

Basic research

    • Characterization of NK cell populations and their importance in (obesity-associated) cancer
    • How do metabolic processes influence NK cells and their anti-cancer activity?
    • Role of adipose tissue for cancer biology and immune responses
    Translational research

      • Development of NK cell focused cell therapies
      • Analysis and application of physical activity and nutritional interventions to modulate NK cell activity in cancer patients
      Clinical research

      • Do metabolic factors such as obesity and metaflammation influence cancer immunotherapy?
      • Nutritional interventions in immunotherapy and stem cell transplantation
      • Combination of targeted / local therapies with systemic immunotherapies (in cooperation with the RIO consortium)
      • Systematic reviews on cell- and immunotherapeutic treatment regimens (in cooperation with the Cochrane Haematological Malignancies Group)
      Cooperations

      • Prof. Dr. Jens C. Brüning, Max-Planck-Institute for Metabolism Research, Cologne Germany
      • Priv.-Doz. Dr. Max Schlaak, Department for Dermatology und Venerology, University Hospital of Cologne, Germany
      • Priv.-Doz. Dr. F. Thomas Wunderlich, Max-Planck-Institute for Metabolism Research, Cologne, Germany
      • Dr. J. Andrew Pospisilik, Max-Planck-Institute for Immunobiology, Freiburg, Germany
      • Priv.-Doz. Dr. Peter Frommolt, CECAD Bioinformatic Core Facility, Cologne, Germany
      • Prof. Dr. Rudolf Stadler, Department for Dermatology und Venerology, J. Wessling Hospital Minden, Germany
      • Prof. Dr. Alfred Zippelius, Department of Medical Oncology, Tumorimmunology, University Hospital Basel, Switzerland
      • Prof. Dr. Veronika Sexl, Institute for Pharmakology and Toxicology, University of Veterinary Medicine, Vienna, Austria
      • Prof. Dr. Bojan Polic, Institute for Histology und Embryology, University of Rijeka, Croatia
      Selected Recent Publications

      Theurich S, Tsaousidou E, Hanssen R, Lempradl AM, Mauer J, Timper K, Schilbach K, Folz-Donahue K, Heilinger C, Sexl V, Pospisilik JA, Wunderlich FT, Brüning JC. IL-6/Stat3-Dependent Induction of Distinct, Obesity-Associated Natural Killer Cells Deteriorates Energy and Glucose Homeostasis. Cell Metabolism, 2017 (in press) IF: 17.897

      Xu E, Pereira MMA, Karakasilioti I, Theurich S, Al-Maarri M, Rappl G, Waisman A, Wunderlich FT, Brüning JC. Temporal and tissue-specific requirements for T-lymphocyte IL-6 signaling in obesity-associated inflammation and insulin resistance, Nature Communications, 2017 (in press) IF: 12.0

      Theurich S, Rothschild SI, Hoffmann M, Fabri M, Sommer A, Garcia-Marquez M, Thelen M, Schill C; Merki R, Schmid T, Koeberle D, Zippelius A, Baues C, Mauch C, Tigges C, Kreuter A, Borggrefe J, von Bergwelt-Baildon M, Schlaak M. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunology Research, 2016 June IF: 6.66

      Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S, Mauer J, Steculorum SM, Hampel B, Goldau J, Alber J, Förster CY, Eming SA, Schwaninger M, Ferrara N, Karsenty G, Brüning JC. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity. Cell, 2016 May 5;165(4):882-95. IF: 28.71

      Wensveen FM, Jelencic V, Valentić S, Šestan M, Turk Wensveen T, Theurich S, Glasner A, Mendrila D, Štimac D, Wunderlich FT, Brüning JC, Mandelboim O and Polić B. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. Nature Immunology, 2015 March IF: 24.97

      Theurich S, Schlaak M, Steguweit H, Heukamp LC, Wennhold K, Kurschat P, et al. Targeting Tumor-Infiltrating B Cells in Cutaneous T-Cell Lymphoma. Journal of Clinical Oncology, 2014. Oct 27. IF: 17.88

      Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Brönneke HS, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Brüning JC. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nature Immunology. 2014;15(5):423-30. IF: 24.97

      Theurich S, Malcher J, Wennhold K, Shimabukuro-Vornhagen A, Chemnitz J, Holtick U, et al. Brentuximab vedotin combined with donor lymphocyte infusions for early relapse of Hodgkin lymphoma after allogeneic stem-cell transplantation induces tumor-specific immunity and sustained clinical remission. Journal of Clinical Oncology, 2013;31(5):e59-63. IF: 18.37

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