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Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity
Cancer treatments have been revolutionized by the emergence of immune checkpoint blockade therapies. However, only a minority of patients with various tumor types have benefited from such treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment hold great pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956510/ https://www.ncbi.nlm.nih.gov/pubmed/35145233 http://dx.doi.org/10.1038/s41388-022-02201-4 |
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author | Zhang, Tao Wang, Yu Li, Qing Lin, Liangyu Xu, Chunliang Xue, Yueqing Hu, Mingyuan Shi, Yufang Wang, Ying |
author_facet | Zhang, Tao Wang, Yu Li, Qing Lin, Liangyu Xu, Chunliang Xue, Yueqing Hu, Mingyuan Shi, Yufang Wang, Ying |
author_sort | Zhang, Tao |
collection | PubMed |
description | Cancer treatments have been revolutionized by the emergence of immune checkpoint blockade therapies. However, only a minority of patients with various tumor types have benefited from such treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment hold great promises. Here, we created IFNα-overexpressing mesenchymal stromal cells (IFNα-MSCs). Upon direct injection into tumors, we found that these cells are powerful in eliminating several types of tumors. Interestingly, the intra-tumoral injection of IFNα-MSCs could also induce specific anti-tumor effects on distant tumors. These IFNα-MSCs promoted tumor cells to produce CXCL10, which in turn potentiates the infiltration of CD8(+) T cells in the tumor site. Furthermore, IFNα-MSCs enhanced the expression of granzyme B (GZMB) in CD8(+) T cells and invigorated their cytotoxicity in a Stat3-dependent manner. Genetic ablation of Stat3 in CD8(+) T cells impaired the effect of IFNα-MSCs on GZMB expression. Importantly, the combination of IFNα-MSCs and PD-L1 blockade induced an even stronger anti-tumor immunity. Therefore, IFNα-MSCs represent a novel tumor immunotherapy strategy, especially when combined with PD-L1 blockade. |
format | Online Article Text |
id | pubmed-8956510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89565102022-04-07 Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity Zhang, Tao Wang, Yu Li, Qing Lin, Liangyu Xu, Chunliang Xue, Yueqing Hu, Mingyuan Shi, Yufang Wang, Ying Oncogene Article Cancer treatments have been revolutionized by the emergence of immune checkpoint blockade therapies. However, only a minority of patients with various tumor types have benefited from such treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment hold great promises. Here, we created IFNα-overexpressing mesenchymal stromal cells (IFNα-MSCs). Upon direct injection into tumors, we found that these cells are powerful in eliminating several types of tumors. Interestingly, the intra-tumoral injection of IFNα-MSCs could also induce specific anti-tumor effects on distant tumors. These IFNα-MSCs promoted tumor cells to produce CXCL10, which in turn potentiates the infiltration of CD8(+) T cells in the tumor site. Furthermore, IFNα-MSCs enhanced the expression of granzyme B (GZMB) in CD8(+) T cells and invigorated their cytotoxicity in a Stat3-dependent manner. Genetic ablation of Stat3 in CD8(+) T cells impaired the effect of IFNα-MSCs on GZMB expression. Importantly, the combination of IFNα-MSCs and PD-L1 blockade induced an even stronger anti-tumor immunity. Therefore, IFNα-MSCs represent a novel tumor immunotherapy strategy, especially when combined with PD-L1 blockade. Nature Publishing Group UK 2022-02-10 2022 /pmc/articles/PMC8956510/ /pubmed/35145233 http://dx.doi.org/10.1038/s41388-022-02201-4 Text en © The Author(s) 2022 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 Zhang, Tao Wang, Yu Li, Qing Lin, Liangyu Xu, Chunliang Xue, Yueqing Hu, Mingyuan Shi, Yufang Wang, Ying Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title | Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title_full | Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title_fullStr | Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title_full_unstemmed | Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title_short | Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity |
title_sort | mesenchymal stromal cells equipped by ifnα empower t cells with potent anti-tumor immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956510/ https://www.ncbi.nlm.nih.gov/pubmed/35145233 http://dx.doi.org/10.1038/s41388-022-02201-4 |
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