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Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer
Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137176/ https://www.ncbi.nlm.nih.gov/pubmed/30245691 http://dx.doi.org/10.3389/fimmu.2018.02030 |
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author | Yasmin-Karim, Sayeda Bruck, Patrick T. Moreau, Michele Kunjachan, Sijumon Chen, Gui Zhen Kumar, Rajiv Grabow, Stephanie Dougan, Stephanie K. Ngwa, Wilfred |
author_facet | Yasmin-Karim, Sayeda Bruck, Patrick T. Moreau, Michele Kunjachan, Sijumon Chen, Gui Zhen Kumar, Rajiv Grabow, Stephanie Dougan, Stephanie K. Ngwa, Wilfred |
author_sort | Yasmin-Karim, Sayeda |
collection | PubMed |
description | Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors. |
format | Online Article Text |
id | pubmed-6137176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61371762018-09-21 Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer Yasmin-Karim, Sayeda Bruck, Patrick T. Moreau, Michele Kunjachan, Sijumon Chen, Gui Zhen Kumar, Rajiv Grabow, Stephanie Dougan, Stephanie K. Ngwa, Wilfred Front Immunol Immunology Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors. Frontiers Media S.A. 2018-09-07 /pmc/articles/PMC6137176/ /pubmed/30245691 http://dx.doi.org/10.3389/fimmu.2018.02030 Text en Copyright © 2018 Yasmin-Karim, Bruck, Moreau, Kunjachan, Chen, Kumar, Grabow, Dougan and Ngwa. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Immunology Yasmin-Karim, Sayeda Bruck, Patrick T. Moreau, Michele Kunjachan, Sijumon Chen, Gui Zhen Kumar, Rajiv Grabow, Stephanie Dougan, Stephanie K. Ngwa, Wilfred Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title | Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title_full | Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title_fullStr | Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title_full_unstemmed | Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title_short | Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer |
title_sort | radiation and local anti-cd40 generate an effective in situ vaccine in preclinical models of pancreatic cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137176/ https://www.ncbi.nlm.nih.gov/pubmed/30245691 http://dx.doi.org/10.3389/fimmu.2018.02030 |
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