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Journal of Immunology Research
Volume 2015 (2015), Article ID 789136, 10 pages
Research Article

Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy

1Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
2Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC 27710, USA
3Duke University, Durham, NC 27710, USA
4Duke University School of Medicine, Durham, NC 27710, USA
5Division of Experimental Medicine, Merck, Rahway, NJ 07065, USA
6Durham VA Medical Center, Section of Otolaryngology-Head and Neck Surgery, Durham, NC 27705, USA

Received 28 August 2015; Accepted 8 October 2015

Academic Editor: Roberta Castriconi

Copyright © 2015 Jens Dannull et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Dendritic cell- (DC-) tumor fusion cells stimulate effective in vivo antitumor responses. However, therapeutic approaches are dependent upon the coadministration of exogenous 3rd signals. The purpose of this study was to determine the mechanisms for inadequate 3rd signaling by electrofused DC-tumor cell hybrids. Methods. Murine melanoma cells were fused with DCs derived from C57BL/6 mice. Quantitative real-time PCR (qPCR) was used to determine relative changes in Th (T helper) 1 and Th2 cytokine gene expression. In addition, changes in gene expression of fusion cells were determined by microarray. Last, cytokine secretion by fusion cells upon inhibition of signaling pathways was analyzed by ELISA. Results. qPCR analyses revealed that fusion cells exhibited a downregulation of Th1 associated cytokines IL-12 and IL-15 and an upregulation of the Th2 cytokine IL-4. Microarray studies further showed that the expression of chemokines, costimulatory molecules, and matrix-metalloproteinases was deregulated in fusion cells. Lastly, inhibitor studies demonstrate that inhibition of the PI3K/Akt/mTOR signaling pathway could restore the secretion of bioactive IL-12p70 by fusion cells. Conclusion. Our results suggest that combining fusion cell-based vaccination with administration of inhibitors of the PI3K/Akt/mTOR signaling pathway may enhance antitumor responses in patients.