Research

The primary goal of radiation therapy is to kill tumor cells. Radiation modulates a plethora of cellular signaling mechanisms that could be exploited for therapeutic benefit. Our main research focus is radiation-induced anti-tumor immunogenicity using conventional photons as well as ions at MedAustron – a unique Austrian center for Ion Therapy and Research.

Recent research showed that radiation in combination with immune checkpoint blockade can clear cancer organism-wide, even in advanced metastasized disease. The success of this approach is, however, limited to a subset of cancers and the molecular mechanisms are poorly understood. We aim at pinpointing the molecular mechanisms necessary to kickstart immune system-mediated tumor clearing in those cancers that have not yet benefitted from immunotherapy. Can we identify specific mutations involved in suppression of anti-tumor immunogenicity? Which molecular mechanisms are involved? Is there a link between radiation-induced anti-tumor immunogenicity and DNA repair? Does autophagy play a role? Is tumor neoantigen presentation influenced by the type of radiation? Can we develop treatment strategies based on our findings?

We use a variety of standard as well as advanced molecular biology techniques. Immune-evasion is tightly linked to the tumor microenvironment. To address this important key aspect, we use heterotypic 3D tumor models, consisting of tumor as well as stromal components. Our future work will focus on the establishment of in vivo models and patient liquid biopsies in collaboration with the medical team on site.

Interferon Type 1 – anti-tumor immunogenicity master regulator

Interferon 1β is the key component of successful anti-tumor immunogenicity activation. Our results show that conventional photons or protons stimulate IFN1β only after fractionated radiation regimen, but not after single dose treatment. Our future aim is to investigate whether physically heavier and hence more biologically effective carbon ions can activate IFN1β. In addition, combination treatment with DNA repair inhibitors will be used to induce synthetic lethality.

Dysfunctional STING – a pancreatic cancer villain

Anti-tumor immunogenicity is based on STING-dependent interferon type 1 activation. Many cancers harbor STING mutations, contributing to the immunosuppressive phenotype of most tumors. Radiation alone fails to activate STING in pancreatic cancer cells. Our aim is to identify and employ STING agonists to induce synthetic lethality in combination with radiation.

Hypoxia – shaping an immunosuppressive tumor microenvironment

We have identified hypoxia as a key immunosuppressive factor. We showed that the hypoxic tumor spheroid areas are not quiescent but rather actively express immunosuppressive proteins while suppressing immunogenic tumor microenvironment key players. The impact of hypoxia on radiation-induced anti-tumor immunogenicity is investigated in hypoxic spheroid models.

Team

Sylvia Kerschbaum-Gruber, PhD

Medical University of Vienna
PostDoc

Karin Posch, BSc

Medical University of Vienna
Lab manager

Katharina Stasny, MSc

MedAustron
PhD student

Maximilian Schmid

University of Vienna
Bachelor student

Ana Beatriz Dias, Msc

Medical University of Vienna
PhD student

Dea Slade, PhD

Medical University of Vienna
Principle investigator

Patrick Fischer, BSc

University of Vienna
Master student

Anna Falkner, MSc

Medical University of Vienna
Technical assistant

Elisabeth Mara, BSc

FH Wiener Neustadt
Collaborator

© Kästenbauer/Ettl

Lab pictures

Collaborations

MedAustron

Ion Therapy and Research Center
Wiener Neustadt, AUSTRIA

Sandra DEMARIA

Weill Cornell Medicine
New York, USA

Birgit LOHBERGER

Medical University of Graz
Graz, AUSTRIA

Martin PRUSCHY

University Hospital Zürich
Zürich, SWITZERLAND

FH Wiener Neustadt

Fachhochschule
Wiener Neustadt, AUSTRIA

Contact

Medical University of Vienna
Department of Radiation Oncology
Währinger Gürtel 18-20
1090 Vienna AUSTRIA

MedAustron
Marie-Curie Straße 5
2700 Wiener Neustadt AUSTRIA