Cargando…

CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Xi, Shao, Qianqian, Hao, Shengnan, Zhao, Zhonghua, Wang, Yang, Guo, Xiaofan, He, Ying, Gao, Wenjuan, Mao, Haiting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355131/
https://www.ncbi.nlm.nih.gov/pubmed/28099147
http://dx.doi.org/10.18632/oncotarget.14626
_version_ 1782515474871877632
author Chen, Xi
Shao, Qianqian
Hao, Shengnan
Zhao, Zhonghua
Wang, Yang
Guo, Xiaofan
He, Ying
Gao, Wenjuan
Mao, Haiting
author_facet Chen, Xi
Shao, Qianqian
Hao, Shengnan
Zhao, Zhonghua
Wang, Yang
Guo, Xiaofan
He, Ying
Gao, Wenjuan
Mao, Haiting
author_sort Chen, Xi
collection PubMed
description Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4(+) breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4(+)/CD8(+) T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs). However, CTLA-4 blockade in breast cancer cells could recover DC maturation and cytokine production, elevate antigen-presenting function of DCs, reverse Th1/CTLs response and cytokine secretion. Subsequent study demonstrated that the activation of extracellular-signal regulated kinase and signal transducer and activator of transcription 3 of DCs caused by CTLA-4(+) breast cancer cells were the predominant mechanism of DC suppression. In addition, CTLA-4 blockade treatment also directly inhibited proliferation and induced apoptosis of CTLA-4(+) breast cancer cells. Collectively, CTLA-4 was expressed and functional on human breast cancer cells through influencing maturation and function of DCs in vitro, and CTLA-4 blockage not only recovered the antigen-presenting function of DCs and T-cells activation but also suppressed the biological activity of breast cancer cells themselves. This study highlights the clinical application of CTLA-4 blockade therapy in breast cancer.
format Online
Article
Text
id pubmed-5355131
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-53551312017-04-15 CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function Chen, Xi Shao, Qianqian Hao, Shengnan Zhao, Zhonghua Wang, Yang Guo, Xiaofan He, Ying Gao, Wenjuan Mao, Haiting Oncotarget Research Paper Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4(+) breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4(+)/CD8(+) T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs). However, CTLA-4 blockade in breast cancer cells could recover DC maturation and cytokine production, elevate antigen-presenting function of DCs, reverse Th1/CTLs response and cytokine secretion. Subsequent study demonstrated that the activation of extracellular-signal regulated kinase and signal transducer and activator of transcription 3 of DCs caused by CTLA-4(+) breast cancer cells were the predominant mechanism of DC suppression. In addition, CTLA-4 blockade treatment also directly inhibited proliferation and induced apoptosis of CTLA-4(+) breast cancer cells. Collectively, CTLA-4 was expressed and functional on human breast cancer cells through influencing maturation and function of DCs in vitro, and CTLA-4 blockage not only recovered the antigen-presenting function of DCs and T-cells activation but also suppressed the biological activity of breast cancer cells themselves. This study highlights the clinical application of CTLA-4 blockade therapy in breast cancer. Impact Journals LLC 2017-01-13 /pmc/articles/PMC5355131/ /pubmed/28099147 http://dx.doi.org/10.18632/oncotarget.14626 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Xi
Shao, Qianqian
Hao, Shengnan
Zhao, Zhonghua
Wang, Yang
Guo, Xiaofan
He, Ying
Gao, Wenjuan
Mao, Haiting
CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title_full CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title_fullStr CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title_full_unstemmed CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title_short CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
title_sort ctla-4 positive breast cancer cells suppress dendritic cells maturation and function
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355131/
https://www.ncbi.nlm.nih.gov/pubmed/28099147
http://dx.doi.org/10.18632/oncotarget.14626
work_keys_str_mv AT chenxi ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT shaoqianqian ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT haoshengnan ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT zhaozhonghua ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT wangyang ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT guoxiaofan ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT heying ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT gaowenjuan ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction
AT maohaiting ctla4positivebreastcancercellssuppressdendriticcellsmaturationandfunction