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...

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Autores principales:	Marka R. Crittenden, Lauren Zebertavage, Gwen Kramer, Shelly Bambina, David Friedman, Victoria Troesch, Tiffany Blair, Jason R. Baird, Alejandro Alice, Michael J. Gough
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f487b6ccc674a53808df9b8692dc7ec
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spelling	oai:doaj.org-article:5f487b6ccc674a53808df9b8692dc7ec2021-12-02T11:41:13ZTumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity10.1038/s41598-018-25482-w2045-2322https://doaj.org/article/5f487b6ccc674a53808df9b8692dc7ec2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25482-whttps://doaj.org/toc/2045-2322Abstract 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.Marka R. CrittendenLauren ZebertavageGwen KramerShelly BambinaDavid FriedmanVictoria TroeschTiffany BlairJason R. BairdAlejandro AliceMichael J. GoughNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5f487b6ccc674a53808df9b8692dc7ec
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Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity

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