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miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells
Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833224/ https://www.ncbi.nlm.nih.gov/pubmed/31594465 http://dx.doi.org/10.1098/rsob.190061 |
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author | Zhang, Meng Gao, Dian Shi, Yanmei Wang, Yifan Joshi, Rakesh Yu, Qiongfang Liu, Daheng Alotaibi, Faizah Zhang, Yujuan Wang, Hongmei Li, Qing Zhang, Zhu-Xu Koropatnick, James Min, Weiping |
author_facet | Zhang, Meng Gao, Dian Shi, Yanmei Wang, Yifan Joshi, Rakesh Yu, Qiongfang Liu, Daheng Alotaibi, Faizah Zhang, Yujuan Wang, Hongmei Li, Qing Zhang, Zhu-Xu Koropatnick, James Min, Weiping |
author_sort | Zhang, Meng |
collection | PubMed |
description | Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer remains largely unknown. In this study, downregulation of miRNAs was observed in PD-1-overexpressing CD8(+) T cells using miRNA array analysis of mouse breast cancer homografts. The data reveal that miR-149-3p was predicted to bind the 3'UTRs of mRNAs encoding T-cell inhibitor receptors PD-1, TIM-3, BTLA and Foxp1. Treatment of CD8(+) T cells with an miR-149-3p mimic reduced apoptosis, attenuated changes in mRNA markers of T-cell exhaustion and downregulated mRNAs encoding PD-1, TIM-3, BTLA and Foxp1. On the other hand, T-cell proliferation and secretion of effector cytokines indicative of increased T-cell activation (IL-2, TNF-α, IFN-γ) were upregulated after miR-149-3p mimic treatment. Moreover, the treatment with a miR-149-3p mimic promoted the capacity of CD8(+) T cells to kill targeted 4T1 mouse breast tumour cells. Collectively, these data show that miR-149-3p can reverse CD8(+) T-cell exhaustion and reveal it to be a potential antitumour immunotherapeutic agent in breast cancer. |
format | Online Article Text |
id | pubmed-6833224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-68332242019-11-12 miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells Zhang, Meng Gao, Dian Shi, Yanmei Wang, Yifan Joshi, Rakesh Yu, Qiongfang Liu, Daheng Alotaibi, Faizah Zhang, Yujuan Wang, Hongmei Li, Qing Zhang, Zhu-Xu Koropatnick, James Min, Weiping Open Biol Research Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer remains largely unknown. In this study, downregulation of miRNAs was observed in PD-1-overexpressing CD8(+) T cells using miRNA array analysis of mouse breast cancer homografts. The data reveal that miR-149-3p was predicted to bind the 3'UTRs of mRNAs encoding T-cell inhibitor receptors PD-1, TIM-3, BTLA and Foxp1. Treatment of CD8(+) T cells with an miR-149-3p mimic reduced apoptosis, attenuated changes in mRNA markers of T-cell exhaustion and downregulated mRNAs encoding PD-1, TIM-3, BTLA and Foxp1. On the other hand, T-cell proliferation and secretion of effector cytokines indicative of increased T-cell activation (IL-2, TNF-α, IFN-γ) were upregulated after miR-149-3p mimic treatment. Moreover, the treatment with a miR-149-3p mimic promoted the capacity of CD8(+) T cells to kill targeted 4T1 mouse breast tumour cells. Collectively, these data show that miR-149-3p can reverse CD8(+) T-cell exhaustion and reveal it to be a potential antitumour immunotherapeutic agent in breast cancer. The Royal Society 2019-10-09 /pmc/articles/PMC6833224/ /pubmed/31594465 http://dx.doi.org/10.1098/rsob.190061 Text en © 2019 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Zhang, Meng Gao, Dian Shi, Yanmei Wang, Yifan Joshi, Rakesh Yu, Qiongfang Liu, Daheng Alotaibi, Faizah Zhang, Yujuan Wang, Hongmei Li, Qing Zhang, Zhu-Xu Koropatnick, James Min, Weiping miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title | miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title_full | miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title_fullStr | miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title_full_unstemmed | miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title_short | miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
title_sort | mir-149-3p reverses cd8(+) t-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833224/ https://www.ncbi.nlm.nih.gov/pubmed/31594465 http://dx.doi.org/10.1098/rsob.190061 |
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