Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment
Radiotherapy (RT) is known to have immune-modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti-PD-1 treatment. In abscopal tumor models...
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/714 |
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| author | Michael Rückert Lisa Deloch Benjamin Frey Eberhard Schlücker Rainer Fietkau Udo S. Gaipl |
| author_facet | Michael Rückert Lisa Deloch Benjamin Frey Eberhard Schlücker Rainer Fietkau Udo S. Gaipl |
| author_sort | Michael Rückert |
| collection | DOAJ |
| description | Radiotherapy (RT) is known to have immune-modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti-PD-1 treatment. In abscopal tumor models, we injected mice with B16-F10 melanoma or TS/A mammary tumors. To evaluate the efficiency of RT in combination with HHP vaccines, we locally irradiated only one tumor with 2 × 8 Gy or 3 × 8 Gy. HHP vaccines further retarded the growth of locally irradiated (2 × 8 Gy) tumors. However, HHP vaccination combined with RT failed to induce abscopal anti-tumor immune responses, namely those to non-irradiated tumors, and even partly abrogated those which were induced with RT plus anti-PD-1. In the latter group, the abscopal effects were accompanied by an elevated infiltration of CD8+ T cells, monocytes/macrophages, and dendritic cells. 3 × 8 Gy failed to induce abscopal effects in association with increased expression of immunosuppressive checkpoint molecules compared to 2 × 8 Gy. We conclude that HHP vaccines induce anti-tumor effects, but only if the tumor microenvironment was previously modulated by hypofractionated RT with not too many fractions, but failed to improve RT plus anti-PD-induced abscopal responses that are characterized by distinct immune alterations. |
| first_indexed | 2024-03-09T04:55:48Z |
| format | Article |
| id | doaj.art-1ace3fe4c65a47efab52c34a6a0aff4e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:55:48Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1ace3fe4c65a47efab52c34a6a0aff4e2023-12-03T13:05:37ZengMDPI AGCancers2072-66942021-02-0113471410.3390/cancers13040714Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor MicroenvironmentMichael Rückert0Lisa Deloch1Benjamin Frey2Eberhard Schlücker3Rainer Fietkau4Udo S. Gaipl5Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyInstitute of Process Machinery and Systems Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyRadiotherapy (RT) is known to have immune-modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti-PD-1 treatment. In abscopal tumor models, we injected mice with B16-F10 melanoma or TS/A mammary tumors. To evaluate the efficiency of RT in combination with HHP vaccines, we locally irradiated only one tumor with 2 × 8 Gy or 3 × 8 Gy. HHP vaccines further retarded the growth of locally irradiated (2 × 8 Gy) tumors. However, HHP vaccination combined with RT failed to induce abscopal anti-tumor immune responses, namely those to non-irradiated tumors, and even partly abrogated those which were induced with RT plus anti-PD-1. In the latter group, the abscopal effects were accompanied by an elevated infiltration of CD8+ T cells, monocytes/macrophages, and dendritic cells. 3 × 8 Gy failed to induce abscopal effects in association with increased expression of immunosuppressive checkpoint molecules compared to 2 × 8 Gy. We conclude that HHP vaccines induce anti-tumor effects, but only if the tumor microenvironment was previously modulated by hypofractionated RT with not too many fractions, but failed to improve RT plus anti-PD-induced abscopal responses that are characterized by distinct immune alterations.https://www.mdpi.com/2072-6694/13/4/714radiotherapyvaccinationhigh hydrostatic pressureimmune checkpoint inhibitionabscopal effecttumor-infiltrating immune cells |
| spellingShingle | Michael Rückert Lisa Deloch Benjamin Frey Eberhard Schlücker Rainer Fietkau Udo S. Gaipl Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment Cancers radiotherapy vaccination high hydrostatic pressure immune checkpoint inhibition abscopal effect tumor-infiltrating immune cells |
| title | Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment |
| title_full | Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment |
| title_fullStr | Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment |
| title_full_unstemmed | Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment |
| title_short | Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment |
| title_sort | combinations of radiotherapy with vaccination and immune checkpoint inhibition differently affect primary and abscopal tumor growth and the tumor microenvironment |
| topic | radiotherapy vaccination high hydrostatic pressure immune checkpoint inhibition abscopal effect tumor-infiltrating immune cells |
| url | https://www.mdpi.com/2072-6694/13/4/714 |
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