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Title: Enhancing immunostimulatory function of human embryonic stem cell-derived dendritic cells by CD1d overexpression
Authors: Zeng, J.
Shahbazi, M.
Wu, C.
Toh, H.C.
Wang, S. 
Issue Date: 1-May-2012
Citation: Zeng, J., Shahbazi, M., Wu, C., Toh, H.C., Wang, S. (2012-05-01). Enhancing immunostimulatory function of human embryonic stem cell-derived dendritic cells by CD1d overexpression. Journal of Immunology 188 (9) : 4297-4304. ScholarBank@NUS Repository.
Abstract: Human embryonic stem cell-derived dendritic cells (hESC-DCs) may potentially provide a platform to generate "off-the-shelf" therapeutic cancer vaccines. To apply hESC-DCs for cancer immunotherapy in a semiallogeneic setting, it is crucial for these cells to "jump-start" adaptive antitumor immunity before their elimination by host alloreaction. In this study, we investigated whether CD1d upregulation in hESC-DCs may exploit invariant NKT (iNKT) cell adjuvant activity and boost antitumor immunity. Using a baculoviral vector carrying the CD1d gene, we produced CD1d-overexpressing hESC-DCs and demonstrated that the upreg-ulated CD1d was functional in presenting α-galactosylceramide for iNKT cell expansion. Pulsed with melanoma Ag recognized by T cell 1 peptide, the CD1d-overexpressing hESC-DCs displayed enhanced capability to prime CD8 + T cells without relying on α-galactosylceramide loading. Blocking the CD1d with Ab reduced the immunogenicity, suggesting the importance of hESC-DC and iNKT cell interaction in this context. The CD1d-overexpressing hESC-DCs also induced a proinflammatory cytokine profile that may favor the T cell priming. Moreover, a similar immunostimulatory effect was observed when the CD1d upregulation strategy was applied in human monocyte-derived dendritic cells. Therefore, our study suggests that the upregulation of CD1d in hESC-DCs provides a novel strategy to enhance their immunogenicity. This approach holds potential for advancing the application of hESC-DCs into human cancer immunotherapy. © 2012 by The American Association of Immunologists, Inc.
Source Title: Journal of Immunology
ISSN: 00221767
DOI: 10.4049/jimmunol.1102343
Appears in Collections:Staff Publications

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