mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment
Abstract
1. Introduction
2. Results
2.1. Suppressive Effects of mTORi on the DC Maturation Markers Expressed on BMMCs Could Be Reversed
2.2. Mature BMM-Derived DCs Treated with mTORi Tended to Be Non-Apoptotic
2.3. mTORi-Treated BMM-Derived DCs Could Have Better Abilities of Antigen Presenting and Processing
2.4. In Vitro Tumoricidal Activity of E7-Specific Cytotoxic CD8+ T Lymphocytes Could Be Increased by mTORi-Treated BMM-Derived DCs
2.5. Expression of Apoptotic Molecules, Bad or Bak Can Be Inhibited in BMM-Derived DCs Treated with mTORi
2.6. mTORi Could Enhance the Anti-Tumor Effects of CTGF/E7 DNA Vaccine to Extend the Survivals of Tumor-Bearing Mice
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Cell Line
4.3. Preparation of DNA Construct and DNA Bullet
4.4. Generation of Immature BMM-Derived DCs
4.5. Maturation of BMM-Derived DCs Stimulated by LPS, CTGF/E7 DNA Plasmid and TC-1 Tumor Cells
4.6. Flow Cytometric Analysis of the Surface Markers of BMM-Derived DCs
4.7. In Vitro Apoptosis Assay of BMM-Derived DCs by Flow Cytometric Analyses
4.8. In Vitro Antigen Presentation Ability of BMM-Derived DCs Treated with mTORi
4.9. In Vitro Antigen Processing Ability of BMM-Derived DCs Treated with mTORi
4.10. In Vitro Anti-Tumor Activity of E7-Specific Cytotoxic CD8+ T Lymphocytes Activated by BMM-Derived DCs Treated with mTORi
4.11. Western Blot Analysis of BMM-Derived DCs Treated with mTORi
4.12. In Vivo Tumor Treatment
4.13. MTT Cytotoxicity Assay
4.14. Preparation of Lymphocytes from Tumor-Associated Draining Lymph Nodes and Tumors
4.15. Intracellular Interferon-γ Cytokine and MHC I-Restricted E7 peptide H-2Db Tetramer Staining by Flow Cytometric Analysis
4.16. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Chen, Y.-L.; Lin, H.-W.; Sun, N.-Y.; Yie, J.-C.; Hung, H.-C.; Chen, C.-A.; Sun, W.-Z.; Cheng, W.-F. mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment. Cancers 2019, 11, 617. https://doi.org/10.3390/cancers11050617
Chen Y-L, Lin H-W, Sun N-Y, Yie J-C, Hung H-C, Chen C-A, Sun W-Z, Cheng W-F. mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment. Cancers. 2019; 11(5):617. https://doi.org/10.3390/cancers11050617
Chicago/Turabian StyleChen, Yu-Li, Han-Wei Lin, Nai-Yun Sun, Jr-Chi Yie, Hsueh-Chih Hung, Chi-An Chen, Wei-Zen Sun, and Wen-Fang Cheng. 2019. "mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment" Cancers 11, no. 5: 617. https://doi.org/10.3390/cancers11050617
APA StyleChen, Y.-L., Lin, H.-W., Sun, N.-Y., Yie, J.-C., Hung, H.-C., Chen, C.-A., Sun, W.-Z., & Cheng, W.-F. (2019). mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment. Cancers, 11(5), 617. https://doi.org/10.3390/cancers11050617