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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00805

Tumor cell-based vaccine generated with high hydrostatic pressure synergizes with radiotherapy by generating a favorable anti-tumor immune microenvironment

 Christoph Seitz1,  Michael Rückert1,  Lisa Deloch1,  Eva-Maria Weiss2, Sebastian Utz1, Marika Izydor3,  Nina Ebel4, Eberhard Schlücker5, Rainer Fietkau1,  Udo S. Gaipl1* and  Benjamin Frey1
  • 1Department of Radiation Oncology, University Hospital Erlangen, Germany
  • 2Department of Radiation Oncology and Department of Psychiatri and Psychotherapy, University Hospital Erlangen, Germany
  • 3Institute for Process Machinery and Systems Engineering, University of Erlangen Nuremberg, Germany
  • 4Department of Cardiac Surgery, University Hospital Erlangen, Germany
  • 5Institute of Process Machinery and Systems Engineering, University of Erlangen Nuremberg, Germany

Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)-inactivated tumor cells have been demonstrated to be a promising immunotherapy for solid tumors. We focused on sole injection of tumor cells that were inactivated by HHP and their combination with local radiotherapy (RTx) for in vivo induction of anti-tumor immune responses. HHP-treatment of tumor cells resulted in predominantly necrotic cells with degraded DNA. We confirmed that treatments at 200 MPa or higher completely inhibited the formation of tumor cell colonies in vitro. No tumor growth was seen in vivo after injection of HHP-treated tumor cells. Single vaccination with HHP-killed tumor cells combined with local RTx significantly retarded tumor growth and improved the survival as shown in B16-F10 and CT26 tumor models. In B16-F10 tumors that were irradiated with 2x5Gy and vaccinated once with HHP-killed tumor cells, the amount of natural killer (NK) cells, monocytes/macrophages, CD4+ T cells and NKT cells was significantly increased, while the amount of B cells was significantly decreased. In both models, a trend of increased CD8+ T cell infiltration was observed. Generally, in irradiated tumors high amounts of CD4+ and CD8+ T cells expressing PD-1 were found. We conclude that HHP generates inactivated tumor cells that can be used as a tumor vaccine alone. Moreover, we show for the first time that tumor cell-based vaccine acts synergistically with RTx to significantly retard tumor growth by generating a favorable anti-tumor immune microenvironment.

Keywords: malignant melanoma, colorectal carcinoma, whole cell-based tumor vaccine, High hydrostatic pressure (HHP), immunogenic cancer cell death, Radiotherapy, Immunotherapy, Radioimmunotherapy, Tumor-infiltrating leukocytes, Tumor microenvironment (TME)

Received: 31 Jan 2019; Accepted: 07 Aug 2019.

Copyright: © 2019 Seitz, Rückert, Deloch, Weiss, Utz, Izydor, Ebel, Schlücker, Fietkau, Gaipl and Frey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Udo S. Gaipl, University Hospital Erlangen, Department of Radiation Oncology, Erlangen, 91054, Bavaria, Germany, udo.gaipl@uk-erlangen.de