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The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells
Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16(+), CD1c/BDCA1(+), and BDCA3(+) (CD141(+)) myeloid DCs and possess different phen...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325999/ https://www.ncbi.nlm.nih.gov/pubmed/32655564 http://dx.doi.org/10.3389/fimmu.2020.01267 |
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author | Gu, Fei-fei Zhang, Kai Ma, Li-li Liu, Yang-yang Li, Chang Hu, Yue Yang, Qi-fan Liang, Jin-yan Zeng, Yu-lan Wang, Yan Liu, Li |
author_facet | Gu, Fei-fei Zhang, Kai Ma, Li-li Liu, Yang-yang Li, Chang Hu, Yue Yang, Qi-fan Liang, Jin-yan Zeng, Yu-lan Wang, Yan Liu, Li |
author_sort | Gu, Fei-fei |
collection | PubMed |
description | Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16(+), CD1c/BDCA1(+), and BDCA3(+) (CD141(+)) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3(+) (CD141(+)) DCs have a superior capacity to stimulate allogeneic CD4(+)T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naïve CD4(+) T cells, but contribute to their differentiation. Importantly, BDCA3(+) (CD141(+)) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3(+) (CD141(+)) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines. |
format | Online Article Text |
id | pubmed-7325999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73259992020-07-09 The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells Gu, Fei-fei Zhang, Kai Ma, Li-li Liu, Yang-yang Li, Chang Hu, Yue Yang, Qi-fan Liang, Jin-yan Zeng, Yu-lan Wang, Yan Liu, Li Front Immunol Immunology Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16(+), CD1c/BDCA1(+), and BDCA3(+) (CD141(+)) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3(+) (CD141(+)) DCs have a superior capacity to stimulate allogeneic CD4(+)T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naïve CD4(+) T cells, but contribute to their differentiation. Importantly, BDCA3(+) (CD141(+)) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3(+) (CD141(+)) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines. Frontiers Media S.A. 2020-06-19 /pmc/articles/PMC7325999/ /pubmed/32655564 http://dx.doi.org/10.3389/fimmu.2020.01267 Text en Copyright © 2020 Gu, Zhang, Ma, Liu, Li, Hu, Yang, Liang, Zeng, Wang and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gu, Fei-fei Zhang, Kai Ma, Li-li Liu, Yang-yang Li, Chang Hu, Yue Yang, Qi-fan Liang, Jin-yan Zeng, Yu-lan Wang, Yan Liu, Li The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title | The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title_full | The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title_fullStr | The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title_full_unstemmed | The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title_short | The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells |
title_sort | superior ability of human bdca3(+) (cd141(+)) dendritic cells (dcs) to cross-present antigens derived from necrotic lung cancer cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325999/ https://www.ncbi.nlm.nih.gov/pubmed/32655564 http://dx.doi.org/10.3389/fimmu.2020.01267 |
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