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CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity
Dendritic cells (DCs), as professional antigen-presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448128/ https://www.ncbi.nlm.nih.gov/pubmed/30864713 http://dx.doi.org/10.3892/or.2019.7037 |
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author | Li, Yifan Zhao, Chujun Liu, Jiajing Lu, Zhou Lu, Mingfang Gu, Jie Liu, Ronghua |
author_facet | Li, Yifan Zhao, Chujun Liu, Jiajing Lu, Zhou Lu, Mingfang Gu, Jie Liu, Ronghua |
author_sort | Li, Yifan |
collection | PubMed |
description | Dendritic cells (DCs), as professional antigen-presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T-cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor-bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4(+)T and CD8(+)T cell activation, particularly cytotoxic T cells. All the T cells (NKT, CD4(+)T and CD8(+)T cells) upregulated CD69, CD107a and IFN-γ after the adoptive transfer of CD1d-positive DCs (CD1d(+)DCs) and tumor growth was suppressed. With regard to the mechanism, we revealed that CD1d(+)DCs were concomitant with a higher expression of costimulatory molecules (CD40, CD80 and CD86) and MHCI/II, which are essential for DCs to present antigens to T cells. Consistently, CD1d(+)DCs displayed stronger activation-associated-ERK1/2 and NF-κB signals; whereas JAK2-STAT3/6 signaling was required for maintaining a high level of CD1d on DCs. In lung cancer patients, the antitumor activities of all the T cells were enhanced with the increase of CD1d(+)DCs. Analysis of TCGA data revealed that high levels of CD1d indicated better outcomes for patients. Collectively, CD1d enhanced DC-based antitumor immunity, not only by targeting NKT, but also by activating CD4(+)T and CD8(+)T cells. CD1d(+)DCs may be superior to the bulk population of DCs in cancer immunotherapy. |
format | Online Article Text |
id | pubmed-6448128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-64481282019-04-05 CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity Li, Yifan Zhao, Chujun Liu, Jiajing Lu, Zhou Lu, Mingfang Gu, Jie Liu, Ronghua Oncol Rep Articles Dendritic cells (DCs), as professional antigen-presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T-cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor-bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4(+)T and CD8(+)T cell activation, particularly cytotoxic T cells. All the T cells (NKT, CD4(+)T and CD8(+)T cells) upregulated CD69, CD107a and IFN-γ after the adoptive transfer of CD1d-positive DCs (CD1d(+)DCs) and tumor growth was suppressed. With regard to the mechanism, we revealed that CD1d(+)DCs were concomitant with a higher expression of costimulatory molecules (CD40, CD80 and CD86) and MHCI/II, which are essential for DCs to present antigens to T cells. Consistently, CD1d(+)DCs displayed stronger activation-associated-ERK1/2 and NF-κB signals; whereas JAK2-STAT3/6 signaling was required for maintaining a high level of CD1d on DCs. In lung cancer patients, the antitumor activities of all the T cells were enhanced with the increase of CD1d(+)DCs. Analysis of TCGA data revealed that high levels of CD1d indicated better outcomes for patients. Collectively, CD1d enhanced DC-based antitumor immunity, not only by targeting NKT, but also by activating CD4(+)T and CD8(+)T cells. CD1d(+)DCs may be superior to the bulk population of DCs in cancer immunotherapy. D.A. Spandidos 2019-05 2019-02-28 /pmc/articles/PMC6448128/ /pubmed/30864713 http://dx.doi.org/10.3892/or.2019.7037 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Li, Yifan Zhao, Chujun Liu, Jiajing Lu, Zhou Lu, Mingfang Gu, Jie Liu, Ronghua CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title | CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title_full | CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title_fullStr | CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title_full_unstemmed | CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title_short | CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity |
title_sort | cd1d highly expressed on dcs reduces lung tumor burden by enhancing antitumor immunity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448128/ https://www.ncbi.nlm.nih.gov/pubmed/30864713 http://dx.doi.org/10.3892/or.2019.7037 |
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