Detail

Keywords

Cachexia; Cytotoxicity, Immunologic; Energy Metabolism; Immunosuppression; Immunosuppressive Agents; Lipid Metabolism; Lipid Peroxidation; Myeloid Cells; Obesity; Phospholipids; Tumor Microenvironment

Research interests

Lipid and lipoprotein metabolism and immunosuppression in cancer

Epidemiological data clearly demonstrate that patients suffering from obesity and the metabolic syndrome have a higher risk to develop cancer. For example, chronically elevated plasma insulin as well as leptin levels have been shown to favor tumor growth and progression, resulting in poor prognosis and higher mortality of obese cancer patients. Moreover, immunosuppressive myeloid cell populations accumulate in the tumor microenvironment (TME) of obese cancer patients, thereby fostering tumor growth and progression. By using syngeneic murine tumor models, biochemical and functional cell biological methods as well as immunological assays, my team is dedicated to understand how metabolic perturbations in systemic lipid and lipoprotein metabolism affect the immunosuppressive behavior of myeloid cells in the TME. Specifically, we aim at the identification of novel obesity-related metabolic pathomechanisms that drive the activation and maturation of myeloid-derived suppressor cells (MDSC), thereby acquiring a highly immunosuppressive phenotype resulting in efficient inhibition of the anti-tumor T cell response.

As well, we are intersted in understanding the systemic, metabolic perturbations that occur in the context of cancer-associated cachexia, a wasting syndrome that frequently manifests in patients suffering from tumors of the gastrointestinal tract.

Techniques, methods & infrastructure

Integrated in the Center for Pathobiochemistry and Genetics, my research group uses syngeneic tumor models, primary cell culture, cancer spheroids and immunological tools to analyze myeloid-derived suppressor cell-mediated immunosuppressive mechanisms that suppress anti-tumor T cell activities.

Grants

• Oxidation-specific epitopes as potential regulators of myeloid-derived suppressor cell functionality in cancer (2024)
  Source of Funding: FWF (Austrian Science Fund), Principal Investigator Project
  Principal Investigator
• The functional role of HDL in the tumor microenvironment (2013)
  Source of Funding: FWF (Austrian Science Fund), Erwin Schrödinger Program
  Principal Investigator

Selected publications

1. Oberle, R. et al. (2022) ‘The HDL particle composition determines its antitumor activity in pancreatic cancer’, Life Science Alliance, 5(9), p. e202101317. Available at: https://doi.org/10.26508/lsa.202101317.
2. Fritsch, S.D. et al. (2023) ‘Metabolic support by macrophages sustains colonic epithelial homeostasis’, Cell Metabolism, 35(11), pp. 1931-1943.e8. Available at: https://doi.org/10.1016/j.cmet.2023.09.010.
3. Bauer, R. et al. (2018) ‘Blockade of Myeloid-Derived Suppressor Cell Expansion with All-Trans Retinoic Acid Increases the Efficacy of Antiangiogenic Therapy’, Cancer Research, 78(12), pp. 3220–3232. Available at: https://doi.org/10.1158/0008-5472.can-17-3415.
4. Bauer, R. et al. (2013) ‘The Developing Chicken Yolk Sac Acquires Nutrient Transport Competence by an Orchestrated Differentiation Process of Its Endodermal Epithelial Cells’, Journal of Biological Chemistry, 288(2), pp. 1088–1098. Available at: https://doi.org/10.1074/jbc.m112.393090.
5. Wroblewski, M. et al. (2017) ‘Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B’, Nature Communications, 8(1). Available at: https://doi.org/10.1038/s41467-017-00327-8.