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Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer
Radiation therapy is an important method in tumor treatment with distinct responses. This study aimed to investigate the immune effects of radiation therapy on the syngeneic gastric tumor model. Mouse forestomach carcinoma (MFC) cells were irradiated with different X-ray doses. Cell proliferation wa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674687/ https://www.ncbi.nlm.nih.gov/pubmed/32960261 http://dx.doi.org/10.1093/jrr/rraa077 |
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author | Hong, Sen Bi, MiaoMiao Yu, HaiYao Yan, ZhenKun Wang, HeLei |
author_facet | Hong, Sen Bi, MiaoMiao Yu, HaiYao Yan, ZhenKun Wang, HeLei |
author_sort | Hong, Sen |
collection | PubMed |
description | Radiation therapy is an important method in tumor treatment with distinct responses. This study aimed to investigate the immune effects of radiation therapy on the syngeneic gastric tumor model. Mouse forestomach carcinoma (MFC) cells were irradiated with different X-ray doses. Cell proliferation was determined by clonogenic assay. Gene and protein expression were determined by real-time quantitative PCR and western blot, respectively. The tumor model was established by subcutaneously injecting tumor cells in 615-(H-2 K) mice. Levels of immune-related factors in tumor tissues were determined by immunohistochemistry and flow cytometry. 5 Gy × 3 (three subfractions with 4 h interval) treatment significantly inhibited cell proliferation. Protein expression of stimulator of interferon genes (Sting) and gene expression of IFNB1, TNFα as well as CXCL-9 significantly increased in MFC cells after irradiation. In the MFC mouse model, no obvious tumor regression was observed after irradiation treatment. Further studies showed Sting protein expression, infiltration of dendritic cells and T cells, and significantly increased PD-1/PD-L1 expression in tumor tissues. Moreover, the irradiation treatment activated T cells and enhanced the therapeutic effects of anti-PD1 antibody against MFC tumor. Our data demonstrated that although the MFC tumor was not sensitive to radiation therapy, the tumor microenvironment could be primed after irradiation. Radiation therapy combined with immunotherapy can greatly improve anti-tumor activities in radiation therapy-insensitive tumor models. |
format | Online Article Text |
id | pubmed-7674687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-76746872020-11-24 Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer Hong, Sen Bi, MiaoMiao Yu, HaiYao Yan, ZhenKun Wang, HeLei J Radiat Res Regular Paper Radiation therapy is an important method in tumor treatment with distinct responses. This study aimed to investigate the immune effects of radiation therapy on the syngeneic gastric tumor model. Mouse forestomach carcinoma (MFC) cells were irradiated with different X-ray doses. Cell proliferation was determined by clonogenic assay. Gene and protein expression were determined by real-time quantitative PCR and western blot, respectively. The tumor model was established by subcutaneously injecting tumor cells in 615-(H-2 K) mice. Levels of immune-related factors in tumor tissues were determined by immunohistochemistry and flow cytometry. 5 Gy × 3 (three subfractions with 4 h interval) treatment significantly inhibited cell proliferation. Protein expression of stimulator of interferon genes (Sting) and gene expression of IFNB1, TNFα as well as CXCL-9 significantly increased in MFC cells after irradiation. In the MFC mouse model, no obvious tumor regression was observed after irradiation treatment. Further studies showed Sting protein expression, infiltration of dendritic cells and T cells, and significantly increased PD-1/PD-L1 expression in tumor tissues. Moreover, the irradiation treatment activated T cells and enhanced the therapeutic effects of anti-PD1 antibody against MFC tumor. Our data demonstrated that although the MFC tumor was not sensitive to radiation therapy, the tumor microenvironment could be primed after irradiation. Radiation therapy combined with immunotherapy can greatly improve anti-tumor activities in radiation therapy-insensitive tumor models. Oxford University Press 2020-09-22 /pmc/articles/PMC7674687/ /pubmed/32960261 http://dx.doi.org/10.1093/jrr/rraa077 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Regular Paper Hong, Sen Bi, MiaoMiao Yu, HaiYao Yan, ZhenKun Wang, HeLei Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title | Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title_full | Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title_fullStr | Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title_full_unstemmed | Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title_short | Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer |
title_sort | radiation therapy enhanced therapeutic efficacy of anti-pd1 against gastric cancer |
topic | Regular Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674687/ https://www.ncbi.nlm.nih.gov/pubmed/32960261 http://dx.doi.org/10.1093/jrr/rraa077 |
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