Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment
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)...
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doaj-982bd7a12a1d4196a3f4da3bc9f6a0eb2020-11-25T01:39:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-08-01910.3389/fonc.2019.00805451759Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune MicroenvironmentChristoph Seitz0Michael Rückert1Lisa Deloch2Eva-Maria Weiss3Eva-Maria Weiss4Sebastian Utz5Marika Izydor6Nina Ebel7Eberhard Schlücker8Rainer Fietkau9Udo S. Gaipl10Benjamin Frey11Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyInstitute of Process Machinery and Systems Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Cardiac Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyInstitute of Process Machinery and Systems Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyDendritic 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 pre-dominantly 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 2 × 5Gy 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. 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.https://www.frontiersin.org/article/10.3389/fonc.2019.00805/fullradiotherapyimmunotherapytumor cell-based vaccinehigh hydrostatic pressuremalignant melanomacolorectal carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christoph Seitz Michael Rückert Lisa Deloch Eva-Maria Weiss Eva-Maria Weiss Sebastian Utz Marika Izydor Nina Ebel Eberhard Schlücker Rainer Fietkau Udo S. Gaipl Benjamin Frey |
spellingShingle |
Christoph Seitz Michael Rückert Lisa Deloch Eva-Maria Weiss Eva-Maria Weiss Sebastian Utz Marika Izydor Nina Ebel Eberhard Schlücker Rainer Fietkau Udo S. Gaipl Benjamin Frey Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment Frontiers in Oncology radiotherapy immunotherapy tumor cell-based vaccine high hydrostatic pressure malignant melanoma colorectal carcinoma |
author_facet |
Christoph Seitz Michael Rückert Lisa Deloch Eva-Maria Weiss Eva-Maria Weiss Sebastian Utz Marika Izydor Nina Ebel Eberhard Schlücker Rainer Fietkau Udo S. Gaipl Benjamin Frey |
author_sort |
Christoph Seitz |
title |
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment |
title_short |
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment |
title_full |
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment |
title_fullStr |
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment |
title_full_unstemmed |
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment |
title_sort |
tumor cell-based vaccine generated with high hydrostatic pressure synergizes with radiotherapy by generating a favorable anti-tumor immune microenvironment |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2019-08-01 |
description |
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 pre-dominantly 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 2 × 5Gy 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. 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. |
topic |
radiotherapy immunotherapy tumor cell-based vaccine high hydrostatic pressure malignant melanoma colorectal carcinoma |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.00805/full |
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