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* Department of Melanoma Medical Oncology, Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; and
Department of Immunology, Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
Plasmacytoid dendritic cells (pDC) are capable of producing high levels of type I IFNs upon viral stimulation, and play a central role in modulating innate and adaptive immunity against viral infections. Whereas many studies have assessed myeloid dendritic cells (mDC) in the induction of antitumor immune responses, the role of pDC in antitumor immunity has not been addressed. Moreover, the interaction of pDC with other dendritic cell subsets has not been evaluated. In this study, we analyzed the capacity of pDC in stimulating an Ag-specific T cell response. Immunization of mice with Ag-pulsed, activated pDC significantly augmented Ag-specific CD8+ CTL responses, and protected mice from a subsequent tumor challenge. Immunization with a mixture of activated pDC plus mDC resulted in increased levels of Ag-specific CD8+ T cells and an enhanced antitumor response compared with immunization with either dendritic cell subset alone. Synergy between pDC and mDC in their ability to activate T cells was dependent on MHC I expression by mDC, but not pDC, suggesting that pDC enhanced the ability of mDC to present Ag to T cells. Our results demonstrate that pDC and mDC can interact synergistically to induce an Ag-specific antitumor immune response in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Y.L. and C.L. contributed equally to this work.
2 P.H. and G.W. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Patrick Hwu, Department of Melanoma Medical Oncology, Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; E-mail address: phwu{at}mdanderson.org or Dr. Gang Wang at the current address: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 1401 Rockville Pike, HFM-675, Rockville, MD 20852; E-mail address: wangg{at}cber.fda.gov
4 Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; Flt3L, Flt3 ligand; int, intermediate; mDC, myeloid DC; NP, nucleoprotein.
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