Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice

Abstract 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 d...

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Autores principales: Heng Zhou, Pengfei Yang, Haining Li, Liying Zhang, Jin Li, Tianyi Zhang, Chengyan Sheng, Jufang Wang
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Lenguaje:EN
Publicado: Nature Publishing Group 2021
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spelling oai:doaj.org-article:a10ce986536f4368886a573223230d482021-11-07T12:21:19ZCarbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice10.1038/s41420-021-00731-62058-7716https://doaj.org/article/a10ce986536f4368886a573223230d482021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00731-6https://doaj.org/toc/2058-7716Abstract 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.Heng ZhouPengfei YangHaining LiLiying ZhangJin LiTianyi ZhangChengyan ShengJufang WangNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Heng Zhou
Pengfei Yang
Haining Li
Liying Zhang
Jin Li
Tianyi Zhang
Chengyan Sheng
Jufang Wang
Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice
description Abstract 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 article
author Heng Zhou
Pengfei Yang
Haining Li
Liying Zhang
Jin Li
Tianyi Zhang
Chengyan Sheng
Jufang Wang
author_facet Heng Zhou
Pengfei Yang
Haining Li
Liying Zhang
Jin Li
Tianyi Zhang
Chengyan Sheng
Jufang Wang
author_sort Heng Zhou
title 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_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_sort carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/a10ce986536f4368886a573223230d48
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