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CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity

  • Authors:
    • Yifan Li
    • Chujun Zhao
    • Jiajing Liu
    • Zhou Lu
    • Mingfang Lu
    • Jie Gu
    • Ronghua Liu
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China, Northfield Mount Hermon School, Northfield, MA 01354, USA, Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2679-2688
    |
    Published online on: February 28, 2019
       https://doi.org/10.3892/or.2019.7037
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Zhao C, Liu J, Lu Z, Lu M, Gu J and Liu R: CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity. Oncol Rep 41: 2679-2688, 2019.
APA
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., & Liu, R. (2019). CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity. Oncology Reports, 41, 2679-2688. https://doi.org/10.3892/or.2019.7037
MLA
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., Liu, R."CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity". Oncology Reports 41.5 (2019): 2679-2688.
Chicago
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., Liu, R."CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity". Oncology Reports 41, no. 5 (2019): 2679-2688. https://doi.org/10.3892/or.2019.7037
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Zhao C, Liu J, Lu Z, Lu M, Gu J and Liu R: CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity. Oncol Rep 41: 2679-2688, 2019.
APA
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., & Liu, R. (2019). CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity. Oncology Reports, 41, 2679-2688. https://doi.org/10.3892/or.2019.7037
MLA
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., Liu, R."CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity". Oncology Reports 41.5 (2019): 2679-2688.
Chicago
Li, Y., Zhao, C., Liu, J., Lu, Z., Lu, M., Gu, J., Liu, R."CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity". Oncology Reports 41, no. 5 (2019): 2679-2688. https://doi.org/10.3892/or.2019.7037
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