PD Dr. rer. nat. Rainer Glauben

Scientific Scope

In the tumor microenvironment, the metabolic milieu differs tremendously from healthy tissue. Glycolysis and fatty acid oxidation are out of balance; you find ongoing hypoxia, inflammation and regeneration. In our previous and recent studies, we see a clear effect of unsaturated fatty acids like oleic acid on the functional polarization of myeloid cells into a monocytic MDSC - as well as a TAM-like phenotype. These cells directly affect the efficacy of cytotoxic T cells and are therefore a major factor to improve modern tumor immunotherapies. We could link this phenotype directly to the formation of lipid droplets inside these cells and an increased fatty acid oxidation compared to control groups. To discover the metabolic pathways and switches to modulate myeloid cell phenotypes in the context of tumor but also intestinal inflammation is one of our major projects in the group. Therefore, we will analyze various tumor entities for their fatty acid content as well as the role of lipid droplet bearing macrophages within these tumors.

Future directions

Ultimately, we will develop interventional strategies to reduce the regulatory effect of tumor-associated macrophages in the tumor microenvironment using specific carriers to deliver metabolic inhibitors.

Group members

• Rainer Glauben - PI
• Inka Freise - Technician
• Hsiang-Jung Hsiao - PhD student
• Sophiya Siddiqui - PhD student
• Adrian Huck - PhD student

Selected References

• Wu, H., Han, Y., Rodriguez Sillke, Y., Deng, H., Siddiqui, S., Treese, C., Schmidt, F., Friedrich, M., Keye, J., Wan, J., Qin, Y., Kühl, A. A., Qin, Z., Siegmund, B., & Glauben, R. (2019). "Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages." EMBO molecular medicine, 11(11), e10698.
• Friedrich, M., Gerbeth, L., Gerling, M., Rosenthal, R., Steiger, K., Weidinger, C., Keye, J., Wu, H., Schmidt, F., Weichert, W., Siegmund, B., Glauben, R. (2019) "HDAC inhibitors promote intestinal epithelial regeneration via autocrine TGFβ1 signalling in inflammation." Mucosal Immunol. 2019 May;12(3):656-667. doi: 10.1038/s41385-019-0135-7. Epub 2019 Jan 23. PMID: 30674988
• Wu, H., Weidinger, C., Schmidt, F., Keye, J., Friedrich, M., Yerinde, C., Willimsky, G., Qin, Z., Siegmund, B., Glauben, R. (2017) "Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells." Sci Rep. 2017 Aug 8;7(1):7498. doi: 10.1038/s41598-017-07685-9.
• Schuster, M., Glauben, R., Plaza-Sirvent, C., Schreiber, L., Annemann, M., Floess, S., Kühl, A. A., Clayton, L. K., Sparwasser, T., Schulze-Osthoff, K., Pfeffer, K., Huehn, J., Siegmund, B., & Schmitz, I. (2012). "IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor." Immunity, 37(6), 998–1008.
• Glauben, R., Batra, A., Stroh, T., Erben, U., Fedke, I., Lehr, H.A., Leoni, F., Mascagni, P., Dinarello, C.A., Zeitz, M., Siegmund, B.  (2008). "Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice." Gut. 2008 May;57(5):613-22. doi: 10.1136/gut.2007.134650. Epub 2008 Jan 14. PMID: 18194985