Medical University of Vienna
Department of Surgery
Vienna General Hospital 25.05.002
Anna Spiegel Center of Translational Research
1090 Vienna, Austria
Phone: +43 1 40400-73514
Fax: +43 1 40400-73593
PI Brostjan has a prime interest in cancer cell – stroma interactions, with a particular focus on
- tumor angiogenesis: The projects include basic research on gene and protein regulation in endothelial cells initiated by the interaction with tumor cells, stroma cells or infiltrating cell populations.
- tumor immunology: Further emphasis is placed on the particular role of monocyte subpopulations in the blood of cancer patients and their effect on tumor growth, angiogenesis and immunological response.
The close association with the Clinical Department of Surgery has resulted in an additional focus on translational studies, investigation of patient samples and identification of parameters of prognosis and response prediction.
Changes of monocyte subsets in response to therapy of colorectal cancer. We have previously reported that in metastasized CRC patients a rapid rise in intermediate blood monocytes after the initial treatment cycle correlates with monocytic tumor infiltrates and predicts response to treatment1. We hypothesize that this change in monocyte subsets and infiltration is not merely a reflection of chemotherapy-mediated tumor destruction (initiating debris clearance and tissue remodeling), but has an essential function in treatment efficacy related to immune cell properties and would constitute a therapeutic target. In this project we will further characterize therapy-related monocyte changes and investigate a functional link to treatment efficacy. Monocyte subsets will be isolated from responder and non-responder CRC patients before and after the initial cycle of chemotherapy (with WM and MS, who will focus on neutrophils). We will then determine cell profiles by FACsorting and subsequent single cell transcriptomics and epigenetics (with GE). Fluorescence-labeled human monocyte subsets will be transferred into xenografted NSG-SGM3 or MISTRG mice (with DHB). Fluorescently marked monocytes will be re-isolated from tumors to assess comparative transcript/epigenetic profiles. Candidate regulators for therapeutic monocyte reprogramming will be tested by applying agonists or inhibitors in a CRC mouse model. The results will provide novel insights into monocyte changes introduced by anticancer therapy and identify targets to promote CRC treatment response.
- Schauer, D.; Starlinger, P.; Alidzanovic, L.; Zajc, P.; Maier, T.; Feldman, A.; Padickakudy, R.; Buchberger, E.; Elleder, V.; Spittler, A.; et al. Chemotherapy of Colorectal Liver Metastases Induces a Rapid Rise in Intermediate Blood Monocytes Which Predicts Treatment Response. Oncoimmunology 2016, 5 (6), e1160185. doi.org/10.1080/2162402X.2016.1160185.
- Buchberger, E., D. Payrhuber, M. El Harchi, B. Zagrapan, K. Scheuba, A. Zommer, E. Bugyik, B. Dome, J. B. Kral, W. C. Schrottmaier, G. Schabbauer, P. Petzelbauer, M. Groger, M. Bilban, and C. Brostjan. 2017. Inhibition of the transcriptional repressor complex Bcl-6/BCoR induces endothelial sprouting but does not promote tumor growth. Oncotarget 8: 552-564, doi: 10.18632/oncotarget.13477.
- Schauer, D., P. Starlinger, L. Alidzanovic, P. Zajc, T. Maier, A. Feldman, R. Padickakudy, E. Buchberger, V. Elleder, A. Spittler, J. Stift, L. Pop, B. Gruenberger, T. Gruenberger, and C. Brostjan. 2016. Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response. Oncoimmunology 5: e1160185, doi: 10.1080/2162402x.2016.1160185.
- Alidzanovic, L., P. Starlinger, D. Schauer, T. Maier, A. Feldman, E. Buchberger, J. Stift, U. Koeck, L. Pop, B. Gruenberger, T. Gruenberger, and C. Brostjan. 2016. The VEGF rise in blood of bevacizumab patients is not based on tumor escape but a host-blockade of VEGF clearance. Oncotarget 7: 57197-57212, doi: 10.18632/oncotarget.11084.
- Starlinger, P., L. Alidzanovic, D. Schauer, T. Maier, C. Nemeth, B. Perisanidis, D. Tamandl, B. Gruenberger, T. Gruenberger, and C. Brostjan. 2012. Neoadjuvant bevacizumab persistently inactivates VEGF at the time of surgery despite preoperative cessation. Br J Cancer 107: 961-966, doi: 10.1038/bjc.2012.342.
- Schauer, D., P. Starlinger, C. Reiter, N. Jahn, P. Zajc, E. Buchberger, T. Bachleitner-Hofmann, M. Bergmann, A. Stift, T. Gruenberger, and C. Brostjan. 2012. Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer. PLoS One 7: e44450, doi: 10.1371/journal.pone.0044450.
- Starlinger, P., P. Brugger, D. Schauer, S. Sommerfeldt, D. Tamandl, I. Kuehrer, S. F. Schoppmann, M. Gnant, and C. Brostjan. 2011. Myelosuppression of thrombocytes and monocytes is associated with a lack of synergy between chemotherapy and anti-VEGF treatment. Neoplasia 13: 419-427, doi.
- Brostjan, C., K. Gebhardt, B. Gruenberger, V. Steinrueck, H. Zommer, H. Freudenthaler, S. Roka, and T. Gruenberger. 2008. Neoadjuvant treatment of colorectal cancer with bevacizumab: the perioperative angiogenic balance is sensitive to systemic thrombospondin-1 levels. Clin Cancer Res 14: 2065-2074, doi: 10.1158/1078-0432.ccr-07-4081.