Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells
Abstract
:1. Introduction
2. Results
2.1. Formulation of Lipoprotein and Phosphodiester CpG within Cationic Liposomes
2.2. The Combination of rlipoE7m and POCpG/DOTAP Enhanced CTL Responses
2.3. The Combination of rlipoE7m and POCpG/DOTAP Could Induce Tumor Regression
2.4. The Combination of rlipoE7m and POCpG/DOTAP Could Reduce the Number of regulatory T Cells in Tumors
3. Discussion
4. Materials and Methods
4.1. Recombinant Lipoprotein Preparation
4.2. Liposome Preparation
4.3. Encapsulation Rate and Adsorption Rate Determination
4.4. Analysis of the Expression of Costimulatory Molecules on BMDCs and Plasmacytoid DCs
4.5. Analysis of IFN-γ-Producing CTLs
4.6. Animal and Tumor Model
4.7. Analysis of Tumor-Infiltrating Cells
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
DCs | Dendritic cells |
TLR2 | Toll-like receptor 2 |
HPV | Human papillomavirus |
ODN | Oligodeoxynucleotides |
cDCs | Conventional DCs |
pDCs | Plasmacytoid DCs |
CTL | Cytotoxic T lymphocyte |
PAMP | Pathogen-associated molecular pattern |
NOD | Nucleotide-binding oligomerization domain |
Tregs | Regulatory T cells |
TAMs | Tumor-associated macrophages |
MDSCs | Myeloid-derived suppressor cells |
DOTAP | 1, 2-Dioleoyloxy-3-trimethylammonium propane |
TNF-α | Tumor necrosis factor-α |
IL | Interleukin |
PSCpG | Phosphorothioate CpG ODN |
POCpG | Phosphodiester CpG ODN |
BMDCs | Bone marrow-derived dendritic cells |
CCL2 | C-C motif chemokine ligand 2 |
ROS | Reactive oxygen species |
MAPK | Mitogen-activated protein kinase |
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Shen, K.-Y.; Liu, H.-Y.; Yan, W.-L.; Wu, C.-C.; Lee, M.-H.; Leng, C.-H.; Liu, S.-J. Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells. Cancers 2020, 12, 810. https://doi.org/10.3390/cancers12040810
Shen K-Y, Liu H-Y, Yan W-L, Wu C-C, Lee M-H, Leng C-H, Liu S-J. Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells. Cancers. 2020; 12(4):810. https://doi.org/10.3390/cancers12040810
Chicago/Turabian StyleShen, Kuan-Yin, Hsin-Yu Liu, Wan-Lun Yan, Chiao-Chieh Wu, Ming-Hui Lee, Chih-Hsing Leng, and Shih-Jen Liu. 2020. "Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells" Cancers 12, no. 4: 810. https://doi.org/10.3390/cancers12040810