The M3 Research Center
Malignome, Metabolome and Microbiome

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Adresse: Otfried-Müller-Straße 37
72076 Tübingen

Office

frontend.sr-only_#{element.icon}: +49 7071 29-82518
Michael Lehmann

frontend.sr-only_#{element.icon}: m3-office@med.uni-tuebingen.de

Metabolic regulation and manipulation of immune cell function in tissues

The research group led by Katrin Böttcher explores how immune cell function is modulated by tissue-specific cues and local microenvironments. 

Our aim is to understand mechanisms of immune cell dysfunction in cancer development, progression and resistance to immunotherapy.  Primarily focusing on hepatobiliary malignancies, we investigate the contribution of tissue niches, cellular networks, as well as metabolic and molecular pathways to anti-cancer immune responses. Recent work by us and others has highlighted the role of innate-like mucosal-associated invariant T (MAIT) cells for cancer development. Therefore, in collaboration with our partners at the University of Tübingen and beyond, we explore how microenvironmental changes in diseases that predispose to cancer development, such as metabolic diseases and chronic viral infections, affect the role of MAIT cells in cancer development. Further focus areas of the group include spatial analysis of immune cells in human tissues, as well as engineering and manipulation of immune cell function. 

Our work stands at the intersection of immunology and clinical application, aiming to advance treatments for hepatobiliary cancers and related hepatological conditions.

Dr. Dr. med. habil. Katrin Böttcher

Head of the research group

Katrin Böttcher is a physician scientist interested in understanding how tissue- and disease-specific cues shape the functionality of immune cells in order to develop personalised, immune-targeted therapeutic strategies for solid cancers.
Katrin graduated in Medicine from the University of Bonn in 2013, which was followed by a PhD and postdoc under the supervision of Prof. Massimo Pinzani at University College London (UK) studying immunological and metabolic pathways involved in the pathogenesis of chronic liver disease. In 2018, Katrin returned to Germany and established an independent research group at the TUM University Hospital in Munich, which was supported by several competitive grants from the German research foundation, Else Kröner Fresenius Foundation, German Cancer Aid and Wilhelm Sander Stiftung. Katrin joined the University of Tübingen in 2025 as a consultant physician at the Department of Internal Medicine I and research group leader at the M3 Research Center.

  • Clinical Department of Internal Medicine II, TUM University Hospital, Technical University of Munich

Wissenschaftliche Abbildung zum Forschungsgebiet
Tissue micro-environment
immune modulation
Immuno-metabolism
MAIT cells
as cellular targets for therapy of solid cancers

Selected publications

Publications

  • Gairing SJ, Mildenberger P, Gile J, Artusa F, Scheiner B, Leyh C, Lieb S,Sinner F, Jörg V, Fruendt T, Himmelsbach V, Abedin N, Sahin C, Böttcher K et al. Evaluation of prognostic scores in HCC patients undergoing 1L immunotherapy with atezolizumab and bevacizumab – development and validation of the CABLE score. J Hep Reports 2024. https://doi.org/10.1016/j.jhepr.2024.101295

  • Bauer U, Fuetterer C, Braren RF, Trifonov P, Schmid RM, Böttcher K and Ehmer U. Decreased overall survival in patients with hepatocellular carcinoma during the COVID-19 pandemic. Translational Gastroenterology and Hepatology. https://dx.doi.org/10.21037/tgh-24-54

    *Authors contributed equally

  • Ben Khaled N, Möller M, Jochheim LS, Leyh C, Ehmer U, Böttcher K, Pinter M et al. Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multi-center real world study with focus on bleeding and thromboembolic events. J Hep Reports 2024. https://doi.org/10.1016/j.jhepr.2024.101065

  • Deschler S, Kager J, Erber J, Fricke L, Koyumdzhieva P, Georgieva A, Lahmer T, Wiessner JR, Voit F, Schneider J, Horstmann J, Iakoubov R, Treiber M, Winter C, Ruland J, Busch DH, Knolle PA, Protzer U, Spinner CD, Schmid RM, Quante M and Böttcher K. Mucosal-associated invariant T (MAIT) cells are highly activated and functionally impaired in COVID-19 patients. Viruses 2021. 13(2): 241

  • Böttcher K, Longato L, Marrone G, Mazza G, Ghemtio L, Hall A, Luong TV, Caruso S, Viollet B, Zucman-Rossi J, Pinzani M and Rombouts K. AICAR and Compound C negatively modulate HCC-induced primary human hepatic stellate cell activation in vitro. American Journal of Physiology Gastrointestinal and Liver Physiology 2021. doi.org/10.1152/ajpgi.00262.2020

  • Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A, Maralli M, Longato L, Thanapirom K, Vilia MG, Lombardi B, Crowley C, Crawford M, Karsdal MA, Leeming DJ, Marrone G, Bottcher K, et al. Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-1 Epithelial Mesenchymal Transition. Cells 2019 .10.3390/cells9010083.

  • Böttcher K, Rombouts K, Saffioti F, Roccarina D, Rosselli M, Hall A, Luong T, et al. MAIT cells are chronically activated in patients with autoimmune liver disease and promote pro-fibrogenic hepatic stellate cell activation. Hepatology 2018. 68(1):172-186

  • Alberts R, de Vries EMG, Goode EC, Jiang X, Sampaziotis F, Rombouts K, Böttcher K, et al. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. Gut 2018;67:1517-1524.

  • Marrone G, De Chiara F, Böttcher K, Levi A, Dhar D, Longato L, Mazza G, et al. The adenosine monophosphate-activated protein kinase-vacuolar adenosine triphosphatase-pH axis: A key regulator of the profibrogenic phenotype of human hepatic stellate cells. Hepatology 2018; 68(3):1140-1153

  • Singh HD, Otano I, Rombouts K, Singh KP, Peppa D, Gill US, Böttcher K, et al. TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis. Sci Rep 2017;7:5514.

  • Schölzel K, Schildberg FA, Welz M, Börner C, Geiger S, Kurts C, Heikenwälder M, et al. Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance. J Hepatol 2014;61:600-608.

Reviews

  • Groth C, Wupper S, Gnouamozi GE, Böttcher K and Cerwenka A. HBV/HDV: Viral interplay and innate immune response. Livers 2024. https://doi.org/10.3390/livers4040040

  • Böttcher K, Pinzani M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents. Adv Drug Deliv Rev 2017;121:3-8.