Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity
Abstract Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated b...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25482-w |
| _version_ | 1818754250255106048 |
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| author | Marka R. Crittenden Lauren Zebertavage Gwen Kramer Shelly Bambina David Friedman Victoria Troesch Tiffany Blair Jason R. Baird Alejandro Alice Michael J. Gough |
| author_facet | Marka R. Crittenden Lauren Zebertavage Gwen Kramer Shelly Bambina David Friedman Victoria Troesch Tiffany Blair Jason R. Baird Alejandro Alice Michael J. Gough |
| author_sort | Marka R. Crittenden |
| collection | DOAJ |
| description | Abstract Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment combination relies on a pre-existing immune response to cure tumors, and may not be a solution for patients without pre-existing immunity. |
| first_indexed | 2024-12-18T05:20:16Z |
| format | Article |
| id | doaj.art-5f487b6ccc674a53808df9b8692dc7ec |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:20:16Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5f487b6ccc674a53808df9b8692dc7ec2022-12-21T21:19:41ZengNature PortfolioScientific Reports2045-23222018-05-018111510.1038/s41598-018-25482-wTumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunityMarka R. Crittenden0Lauren Zebertavage1Gwen Kramer2Shelly Bambina3David Friedman4Victoria Troesch5Tiffany Blair6Jason R. Baird7Alejandro Alice8Michael J. Gough9Earle A. Chiles Research Institute, Providence Portland Medical CenterMolecular Microbiology & Immunology, Oregon Health & Science UniversityEarle A. Chiles Research Institute, Providence Portland Medical CenterEarle A. Chiles Research Institute, Providence Portland Medical CenterEarle A. Chiles Research Institute, Providence Portland Medical CenterEarle A. Chiles Research Institute, Providence Portland Medical CenterMolecular Microbiology & Immunology, Oregon Health & Science UniversityEarle A. Chiles Research Institute, Providence Portland Medical CenterEarle A. Chiles Research Institute, Providence Portland Medical CenterEarle A. Chiles Research Institute, Providence Portland Medical CenterAbstract Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment combination relies on a pre-existing immune response to cure tumors, and may not be a solution for patients without pre-existing immunity.https://doi.org/10.1038/s41598-018-25482-w |
| spellingShingle | Marka R. Crittenden Lauren Zebertavage Gwen Kramer Shelly Bambina David Friedman Victoria Troesch Tiffany Blair Jason R. Baird Alejandro Alice Michael J. Gough Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity Scientific Reports |
| title | Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity |
| title_full | Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity |
| title_fullStr | Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity |
| title_full_unstemmed | Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity |
| title_short | Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity |
| title_sort | tumor cure by radiation therapy and checkpoint inhibitors depends on pre existing immunity |
| url | https://doi.org/10.1038/s41598-018-25482-w |
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