Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yifan, Zhao, Chujun, Liu, Jiajing, Lu, Zhou, Lu, Mingfang, Gu, Jie, Liu, Ronghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
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
_version_ 1783408638302355456
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
work_keys_str_mv AT liyifan cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT zhaochujun cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT liujiajing cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT luzhou cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT lumingfang cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT gujie cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity
AT liuronghua cd1dhighlyexpressedondcsreduceslungtumorburdenbyenhancingantitumorimmunity