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Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice
Numerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease ou...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566527/ https://www.ncbi.nlm.nih.gov/pubmed/34732697 http://dx.doi.org/10.1038/s41420-021-00731-6 |
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author | Zhou, Heng Yang, Pengfei Li, Haining Zhang, Liying Li, Jin Zhang, Tianyi Sheng, Chengyan Wang, Jufang |
author_facet | Zhou, Heng Yang, Pengfei Li, Haining Zhang, Liying Li, Jin Zhang, Tianyi Sheng, Chengyan Wang, Jufang |
author_sort | Zhou, Heng |
collection | PubMed |
description | Numerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease outcome. This study analysed the changes in the immune contexture in response to the carbon ion treatment. The murine melanoma B16, MelanA, and S91 tumour models were established in syngeneic immunocompetent mice. Then, the tumours were irradiated with carbon ion beams, and flow cytometry was utilised to observe the immune contexture changes in the bone marrow, peripheral blood, spleen, and tumours. The immune infiltrates in the tumour tissues were further assessed using haematoxylin/eosin staining and immunohistochemistry. The immunoblot detected the expression of proteins associated with the JAK/STAT signalling pathway. The secretion of immune-related cytokines was examined using ELISA. Compared to conventional radiotherapy, particle beams have distinct advantages in cancer therapy. Here, the use of carbon ion beams (5 GyE) for melanoma-bearing mice was found to reduce the population of MDSC in the bone marrow, peripheral blood, and spleen of the animals via a JAK2/STAT3-dependent mechanism. The percentage of CD3(+), CD4(+), CD8(+) T cells, macrophages, and natural killer cells increased after radiation, resulting in reduced tumour growth and prolonged overall survival in the three different mouse models of melanoma. This study, therefore, substantiated that CIRT boosts anti-tumour immune responses via the inhibition of MDSC. |
format | Online Article Text |
id | pubmed-8566527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85665272021-11-16 Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice Zhou, Heng Yang, Pengfei Li, Haining Zhang, Liying Li, Jin Zhang, Tianyi Sheng, Chengyan Wang, Jufang Cell Death Discov Article Numerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease outcome. This study analysed the changes in the immune contexture in response to the carbon ion treatment. The murine melanoma B16, MelanA, and S91 tumour models were established in syngeneic immunocompetent mice. Then, the tumours were irradiated with carbon ion beams, and flow cytometry was utilised to observe the immune contexture changes in the bone marrow, peripheral blood, spleen, and tumours. The immune infiltrates in the tumour tissues were further assessed using haematoxylin/eosin staining and immunohistochemistry. The immunoblot detected the expression of proteins associated with the JAK/STAT signalling pathway. The secretion of immune-related cytokines was examined using ELISA. Compared to conventional radiotherapy, particle beams have distinct advantages in cancer therapy. Here, the use of carbon ion beams (5 GyE) for melanoma-bearing mice was found to reduce the population of MDSC in the bone marrow, peripheral blood, and spleen of the animals via a JAK2/STAT3-dependent mechanism. The percentage of CD3(+), CD4(+), CD8(+) T cells, macrophages, and natural killer cells increased after radiation, resulting in reduced tumour growth and prolonged overall survival in the three different mouse models of melanoma. This study, therefore, substantiated that CIRT boosts anti-tumour immune responses via the inhibition of MDSC. Nature Publishing Group UK 2021-11-03 /pmc/articles/PMC8566527/ /pubmed/34732697 http://dx.doi.org/10.1038/s41420-021-00731-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhou, Heng Yang, Pengfei Li, Haining Zhang, Liying Li, Jin Zhang, Tianyi Sheng, Chengyan Wang, Jufang Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title | Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title_full | Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title_fullStr | Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title_full_unstemmed | Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title_short | Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
title_sort | carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566527/ https://www.ncbi.nlm.nih.gov/pubmed/34732697 http://dx.doi.org/10.1038/s41420-021-00731-6 |
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