Daria Klusa

Co-evolution of circulating tumor cells and immune cells within the blood of prostate cancer patients under local ablative radiotherapy

Abstract

Precise imaging technologies enable early detection of metastatic spread and the precise delivery of a defined irradiation dose to active metastatic lesions in prostate cancer patients. To date, prognostic biomarker guiding clinical decisions for ablative radiotherapy treatment planning is not available. Within the present study, we hypothesized that the amount, phenotype, dynamics of circulating tumor cells (CTCs) may have prognostic potential and that these features are influenced by interactions of CTCs with immune cells. We identified the chemokine receptor CXCR4 is a determinant for co-occurrence of bone and lymph node metastases in those patients. This was accompanied by increasing plasma CCL2 and osteoprotegerin concentrations as well as pro-inflammatory monocytes in response to radiotherapy. To investigate the immune phenotype and its alteration in response radiotherapy, we applied a 33-maker mass cytometry panel including nine known pro-inflammatory cytokines such as CCL2. In summary, we found that prostate CTCs may be guided through CXCR4- and CCL2-mediated signaling into the bone and support colonization. This is currently validated  in a prospective trial of oligo-metastatic prostate cancer patients.

Biosketch 

2019 – present: PhD Studies,  Faculty of Medicine Carl Gustav Carus and The University Hospital Dresden, Technical University of Dresden, Germany – Thesis tittle: Identification of prognostic signatures for bone metastasis-initiating and radioresistant tumor cells in prostate cancer

2017 –2018: Research Trainee, Cell Cycle & Cancer Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA2015 – 2018: Master Studies, Medical Biotechnology, Faculty of Biotechnology, University of Wroclaw, Poland

Contact/Affiliation

National Center for Tumor Diseases (NCT), Dresden, Germany,

Collaborations

  1. Claudia Peitzsch (Mass Cytometry Facility, Center for Regenerative Therapies Dresden (CRTD), Technical University Dresden)
  2. Ina Kurth, Michael Baumann (German Cancer Research Center DKFZ, Heidelberg, Germany)
  3. Fabian Lohaus, Annett Linge, Tobias Hölscher, Mechthild Krause, Anna Dubrovska (OncoRay – National Center for Radiation Research in Oncology, Dresden, Germany)
  4. Andre Franken, Mahdi Rivandi, Hans Neubauer (Department of Obstetrics and Gynecology, Medical Faculty and University Hospital of the Heinrich-Heine University, Düsseldorf, Germany)
  5. Anne Offermann, Sven Perner (Institute of Pathology, University Hospital Schleswig Holstein, Lübeck, Germany)
  6. Bernhard Polzer (Division of Personalized Tumor Therapy, Fraunhofer-Institute for Toxicology and Experimental Medicine, Regensburg, Germany)
  7. Michael Kücken (Department for Innovative Methods of Computing, Center for Principal component Information Services and High-Performance Computing ZIH, Technische Universität, Dresden, Germany)