Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy
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 electrofus...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/789136 |
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| author | Jens Dannull Chunrui Tan Christine Farrell Cynthia Wang Scott Pruitt Smita K. Nair Walter T. Lee |
| author_facet | Jens Dannull Chunrui Tan Christine Farrell Cynthia Wang Scott Pruitt Smita K. Nair Walter T. Lee |
| author_sort | Jens Dannull |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-acca9bb4358440edb6f6999bbd6d063c |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-acca9bb4358440edb6f6999bbd6d063c2025-08-20T03:38:55ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/789136789136Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer ImmunotherapyJens Dannull0Chunrui Tan1Christine Farrell2Cynthia Wang3Scott Pruitt4Smita K. Nair5Walter T. Lee6Department of Surgery, Duke University Medical Center, Durham, NC 27710, USADepartment of Surgery, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC 27710, USADuke University, Durham, NC 27710, USADuke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USADepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USADepartment of Surgery, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC 27710, USABackground. 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.http://dx.doi.org/10.1155/2015/789136 |
| spellingShingle | Jens Dannull Chunrui Tan Christine Farrell Cynthia Wang Scott Pruitt Smita K. Nair Walter T. Lee Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy Journal of Immunology Research |
| title | Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy |
| title_full | Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy |
| title_fullStr | Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy |
| title_full_unstemmed | Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy |
| title_short | Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy |
| title_sort | gene expression profile of dendritic cell tumor cell hybrids determined by microarrays and its implications for cancer immunotherapy |
| url | http://dx.doi.org/10.1155/2015/789136 |
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