請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90325完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 牟昀 | zh_TW |
| dc.contributor.advisor | Yun Mou | en |
| dc.contributor.author | 鄭庭葦 | zh_TW |
| dc.contributor.author | Ting-Wei Cheng | en |
| dc.date.accessioned | 2023-09-26T16:16:33Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-09-26 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-07-26 | - |
| dc.identifier.citation | 1 Bishop, D. G. & Work, E. An Extracellular Glycolipid Produced by Escherichia Coli Grown under Lysine-Limiting Conditions. Biochem J 96, 567-+ (1965). https://doi.org:DOI 10.1042/bj0960567
2 Knox, K. W., Vesk, M. & Work, E. Relation between Excreted Lipopolysaccharide Complexes and Surface Structures of a Lysine-Limited Culture of Escherichia Coli. Journal of Bacteriology 92, 1206-& (1966). https://doi.org:Doi 10.1128/Jb.92.4.1206-1217.1966 3 Mergenhagen, S. E., Bladen, H. A. & Hsu, K. C. Electron microscopic localization of endotoxic lipopolysaccharide in gram-negative organisms. Ann N Y Acad Sci 133, 279-291 (1966). https://doi.org:10.1111/j.1749-6632.1966.tb52371.x 4 Chatterj.Sn & Das, J. Electron Microscopic Observations on Excretion of Cell-Wall Materials by Vibrio Cholerae. J Gen Microbiol 49, 1-& (1967). 5 Rothfield, L. & Pearlman.M. Synthesis and Assembly of Bacterial Membrane Components - a Lipopolysaccharide-Phospholipid-Protein Complex Excreted by Living Bacteria. Journal of Molecular Biology 44, 477-+ (1969). https://doi.org:Doi 10.1016/0022-2836(69)90374-X 6 Devoe, I. W. & Gilchrist, J. E. Pili on Meningococci from Primary Cultures of Nasopharyngeal Carriers and Cerebrospinal-Fluid of Patients with Acute Disease. J Exp Med 141, 297-305 (1975). https://doi.org:DOI 10.1084/jem.141.2.297 7 Blenkiron, C. et al. Uropathogenic Escherichia coli Releases Extracellular Vesicles That Are Associated with RNA. PLoS One 11, e0160440 (2016). https://doi.org:10.1371/journal.pone.0160440 8 Vanaja, S. K. et al. Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation. Cell 165, 1106-1119 (2016). https://doi.org:10.1016/j.cell.2016.04.015 9 Horstman, A. L. & Kuehn, M. J. Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles. Journal of Biological Chemistry 275, 12489-12496 (2000). https://doi.org:DOI 10.1074/jbc.275.17.12489 10 Perez-Cruz, C., Delgado, L., Lopez-Iglesias, C. & Mercade, E. Outer-inner membrane vesicles naturally secreted by gram-negative pathogenic bacteria. PLoS One 10, e0116896 (2015). https://doi.org:10.1371/journal.pone.0116896 11 Amalia, L. & Tsai, S. L. Functionalization of OMVs for Biocatalytic Applications. Membranes (Basel) 13 (2023). https://doi.org:10.3390/membranes13050459 12 Schwechheimer, C. & Kuehn, M. J. Synthetic effect between envelope stress and lack of outer membrane vesicle production in Escherichia coli. J Bacteriol 195, 4161-4173 (2013). https://doi.org:10.1128/JB.02192-12 13 Maredia, R. et al. Vesiculation from Pseudomonas aeruginosa under SOS. ScientificWorldJournal 2012, 402919 (2012). https://doi.org:10.1100/2012/402919 14 Manning, A. J. & Kuehn, M. J. Contribution of bacterial outer membrane vesicles to innate bacterial defense. Bmc Microbiology 11 (2011). https://doi.org:Artn 25810.1186/1471-2180-11-258 15 Elhenawy, W., Debelyy, M. O. & Feldman, M. F. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. mBio 5, e00909-00914 (2014). https://doi.org:10.1128/mBio.00909-14 16 Fulsundar, S. et al. Gene transfer potential of outer membrane vesicles of Acinetobacter baylyi and effects of stress on vesiculation. Appl Environ Microbiol 80, 3469-3483 (2014). https://doi.org:10.1128/AEM.04248-13 17 Mashburn-Warren, L. M. & Whiteley, M. Special delivery: vesicle trafficking in prokaryotes. Mol Microbiol 61, 839-846 (2006). https://doi.org:10.1111/j.1365-2958.2006.05272.x 18 Schwechheimer, C. & Kuehn, M. J. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol 13, 605-619 (2015). https://doi.org:10.1038/nrmicro3525 19 Fitzgerald, K. A. & Kagan, J. C. Toll-like Receptors and the Control of Immunity. Cell 180, 1044-1066 (2020). https://doi.org:10.1016/j.cell.2020.02.041 20 Sutmuller, R. P. et al. Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest 116, 485-494 (2006). https://doi.org:10.1172/JCI25439 21 Bellocchio, S. et al. TLRs govern neutrophil activity in aspergillosis. J Immunol 173, 7406-7415 (2004). https://doi.org:10.4049/jimmunol.173.12.7406 22 Sun, C. M., Deriaud, E., Leclerc, C. & Lo-Man, R. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity 22, 467-477 (2005). https://doi.org:10.1016/j.immuni.2005.02.008 23 McClure, R. & Massari, P. TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens. Front Immunol 5, 386 (2014). https://doi.org:10.3389/fimmu.2014.00386 24 Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11, 373-384 (2010). https://doi.org:10.1038/ni.1863 25 Blasius, A. L. & Beutler, B. Intracellular toll-like receptors. Immunity 32, 305-315 (2010). https://doi.org:10.1016/j.immuni.2010.03.012 26 Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783-801 (2006). https://doi.org:10.1016/j.cell.2006.02.015 27 Akira, S. & Takeda, K. Toll-like receptor signalling. Nat Rev Immunol 4, 499-511 (2004). https://doi.org:10.1038/nri1391 28 Shen, H., Tesar, B. M., Walker, W. E. & Goldstein, D. R. Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. J Immunol 181, 1849-1858 (2008). https://doi.org:10.4049/jimmunol.181.3.1849 29 Yamamoto, M. et al. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169, 6668-6672 (2002). https://doi.org:10.4049/jimmunol.169.12.6668 30 Ullah, M. O., Sweet, M. J., Mansell, A., Kellie, S. & Kobe, B. TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target. J Leukoc Biol 100, 27-45 (2016). https://doi.org:10.1189/jlb.2RI1115-531R 31 Ivashkiv, L. B. & Donlin, L. T. Regulation of type I interferon responses. Nat Rev Immunol 14, 36-49 (2014). https://doi.org:10.1038/nri3581 32 Duan, T., Du, Y., Xing, C., Wang, H. Y. & Wang, R.-F. Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity. Frontiers in Immunology 13 (2022). https://doi.org:10.3389/fimmu.2022.812774 33 Mancini, F., Rossi, O., Necchi, F. & Micoli, F. OMV Vaccines and the Role of TLR Agonists in Immune Response. Int J Mol Sci 21 (2020). https://doi.org:10.3390/ijms21124416 34 Kang, J. Y. et al. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 31, 873-884 (2009). https://doi.org:10.1016/j.immuni.2009.09.018 35 Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103 (2001). https://doi.org:Doi 10.1038/35074106 36 Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 (2000). https://doi.org:Doi 10.1038/35047123 37 Beutler, B. & Rietschel, E. T. Innate immune sensing and its roots: the story of endotoxin. Nature Reviews Immunology 3, 169-176 (2003). https://doi.org:10.1038/nri1004 38 Whitfield, C., Williams, D. M. & Kelly, S. D. Lipopolysaccharide O-antigens-bacterial glycans made to measure. J Biol Chem 295, 10593-10609 (2020). https://doi.org:10.1074/jbc.REV120.009402 39 Duerr, C. U. et al. O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells. PLoS Pathog 5, e1000567 (2009). https://doi.org:10.1371/journal.ppat.1000567 40 Frirdich, E. & Whitfield, C. Lipopolysaccharide inner core oligosaccharide structure and outer membrane stability in human pathogens belonging to the Enterobacteriaceae. J Endotoxin Res 11, 133-144 (2005). https://doi.org:10.1179/096805105X46592 41 Lu, Y. C., Yeh, W. C. & Ohashi, P. S. LPS/TLR4 signal transduction pathway. Cytokine 42, 145-151 (2008). https://doi.org:10.1016/j.cyto.2008.01.006 42 Bachmann, M. F. & Jennings, G. T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10, 787-796 (2010). https://doi.org:10.1038/nri2868 43 Li, M. et al. Bacterial outer membrane vesicles as a platform for biomedical applications: An update. J Control Release 323, 253-268 (2020). https://doi.org:10.1016/j.jconrel.2020.04.031 44 Swain, S. L., McKinstry, K. K. & Strutt, T. M. Expanding roles for CD4(+) T cells in immunity to viruses. Nat Rev Immunol 12, 136-148 (2012). https://doi.org:10.1038/nri3152 45 Gorringe, A. R. & Pajon, R. Bexsero: a multicomponent vaccine for prevention of meningococcal disease. Hum Vaccin Immunother 8, 174-183 (2012). https://doi.org:10.4161/hv.18500 46 Awate, S., Babiuk, L. A. & Mutwiri, G. Mechanisms of action of adjuvants. Front Immunol 4, 114 (2013). https://doi.org:10.3389/fimmu.2013.00114 47 Tan, K., Li, R., Huang, X. & Liu, Q. Outer Membrane Vesicles: Current Status and Future Direction of These Novel Vaccine Adjuvants. Front Microbiol 9, 783 (2018). https://doi.org:10.3389/fmicb.2018.00783 48 Miyaji, E. N., Carvalho, E., Oliveira, M. L., Raw, I. & Ho, P. L. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants. Braz J Med Biol Res 44, 500-513 (2011). https://doi.org:10.1590/s0100-879x2011007500064 49 Sardinas, G., Reddin, K., Pajon, R. & Gorringe, A. Outer membrane vesicles of Neisseria lactamica as a potential mucosal adjuvant. Vaccine 24, 206-214 (2006). https://doi.org:10.1016/j.vaccine.2005.07.064 50 Daleke-Schermerhorn, M. H. et al. Decoration of outer membrane vesicles with multiple antigens by using an autotransporter approach. Appl Environ Microbiol 80, 5854-5865 (2014). https://doi.org:10.1128/AEM.01941-14 51 Gujrati, V. et al. Bioengineered Bacterial Outer Membrane Vesicles as Cell-Specific Drug-Delivery Vehicles for Cancer Therapy. Acs Nano 8, 1525-1537 (2014). https://doi.org:10.1021/nn405724x 52 McCarthy, E. F. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J 26, 154-158 (2006). 53 Kim, O. Y. et al. Bacterial outer membrane vesicles suppress tumor by interferon-gamma-mediated antitumor response. Nat Commun 8, 626 (2017). https://doi.org:10.1038/s41467-017-00729-8 54 Urban-Wojciuk, Z. et al. The Role of TLRs in Anti-cancer Immunity and Tumor Rejection. Front Immunol 10, 2388 (2019). https://doi.org:10.3389/fimmu.2019.02388 55 Imanishi, T. et al. Cutting edge: TLR2 directly triggers Th1 effector functions. J Immunol 178, 6715-6719 (2007). https://doi.org:10.4049/jimmunol.178.11.6715 56 Salerno, F., Freen-van Heeren, J. J., Guislain, A., Nicolet, B. P. & Wolkers, M. C. Costimulation through TLR2 Drives Polyfunctional CD8(+) T Cell Responses. J Immunol 202, 714-723 (2019). https://doi.org:10.4049/jimmunol.1801026 57 Freen-van Heeren, J. J. Toll-like receptor-2/7-mediated T cell activation: An innate potential to augment CD8(+) T cell cytokine production. Scand J Immunol 93, e13019 (2021). https://doi.org:10.1111/sji.13019 58 Zhang, E., Ma, Z. & Lu, M. Contribution of T- and B-cell intrinsic toll-like receptors to the adaptive immune response in viral infectious diseases. Cell Mol Life Sci 79, 547 (2022). https://doi.org:10.1007/s00018-022-04582-x 59 Greten, F. R. & Grivennikov, S. I. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity 51, 27-41 (2019). https://doi.org:10.1016/j.immuni.2019.06.025 60 Ribatti, D. & Tamma, R. A revisited concept. Tumors: Wounds that do not heal. Crit Rev Oncol Hematol 128, 65-69 (2018). https://doi.org:10.1016/j.critrevonc.2018.05.016 61 Zhou, H., Jiang, M., Yuan, H., Ni, W. & Tai, G. Dual roles of myeloid-derived suppressor cells induced by Toll-like receptor signaling in cancer. Oncol Lett 21, 149 (2021). https://doi.org:10.3892/ol.2020.12410 62 Lu, H. TLR Agonists for Cancer Immunotherapy: Tipping the Balance between the Immune Stimulatory and Inhibitory Effects. Front Immunol 5, 83 (2014). https://doi.org:10.3389/fimmu.2014.00083 63 Munn, D. H. & Mellor, A. L. IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance. Trends Immunol 37, 193-207 (2016). https://doi.org:10.1016/j.it.2016.01.002 64 Wolfle, S. J. et al. PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur J Immunol 41, 413-424 (2011). https://doi.org:10.1002/eji.201040979 65 Greulich, B. M., Plotnik, J. P., Jerde, T. J. & Hollenhorst, P. C. Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target. NAR Cancer 3, zcaa046 (2021). https://doi.org:10.1093/narcan/zcaa046 66 Chen, X., Zhang, Y. & Fu, Y. The critical role of Toll-like receptor-mediated signaling in cancer immunotherapy. Medicine in Drug Discovery 14 (2022). https://doi.org:10.1016/j.medidd.2022.100122 67 Sperandeo, P., Martorana, A. M. & Polissi, A. Lipopolysaccharide biogenesis and transport at the outer membrane of Gram-negative bacteria. Biochim Biophys Acta Mol Cell Biol Lipids 1862, 1451-1460 (2017). https://doi.org:10.1016/j.bbalip.2016.10.006 68 Alexander, C. & Rietschel, E. T. Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res 7, 167-202 (2001). 69 Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J. & Gusovsky, F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 274, 10689-10692 (1999). https://doi.org:10.1074/jbc.274.16.10689 70 Rosso, M. et al. LPS-Induced Cytokine Production in Human Monocytes and Macrophages. Crit Rev Immunol 31, 379-446 (2011). https://doi.org:DOI 10.1615/CritRevImmunol.v31.i5.20 71 Cohen, J. The immunopathogenesis of sepsis. Nature 420, 885-891 (2002). https://doi.org:10.1038/nature01326 72 Schulte, W., Bernhagen, J. & Bucala, R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view. Mediators Inflamm 2013, 165974 (2013). https://doi.org:10.1155/2013/165974 73 Chicoine, M. R., Won, E. K. & Zahner, M. C. Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme. Neurosurgery 48, 607-614; discussion 614-605 (2001). https://doi.org:10.1097/00006123-200103000-00032 74 Hattori, Y., Szabo, C., Gross, S. S., Thiemermann, C. & Vane, J. R. Lipid-a and the Lipid-a Analog Antitumor Compound Ono-4007 Induce Nitric-Oxide Synthase in-Vitro and in-Vivo. Eur J Pharm-Molec Ph 291, 83-90 (1995). https://doi.org:Doi 10.1016/0922-4106(95)90128-0 75 Andreani, V., Gatti, G., Simonella, L., Rivero, V. & Maccioni, M. Activation of Toll-like receptor 4 on tumor cells in vitro inhibits subsequent tumor growth in vivo. Cancer Res 67, 10519-10527 (2007). https://doi.org:10.1158/0008-5472.CAN-07-0079 76 de Bono, J. S. et al. Phase I study of ONO-4007, a synthetic analogue of the lipid a moiety of bacterial lipopolysaccharide. Clin Cancer Res 6, 397-405 (2000). 77 Goto, S. et al. Intradermal administration of lipopolysaccharide in treatment of human cancer. Cancer Immunol Immun 42, 255-261 (1996). https://doi.org:DOI 10.1007/s002620050279 78 Park, B. S. & Lee, J. O. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med 45, e66 (2013). https://doi.org:10.1038/emm.2013.97 79 Maeshima, N. & Fernandez, R. C. Recognition of lipid A variants by the TLR4-MD-2 receptor complex. Front Cell Infect Microbiol 3, 3 (2013). https://doi.org:10.3389/fcimb.2013.00003 80 Tsuneyoshi, N. et al. Penta-acylated lipopolisaccharide binds to murine MD-2 but does not induce the oligomerization of TLR4 required for signal transduction. Cell Immunol 244, 57-64 (2006). https://doi.org:10.1016/j.cellimm.2007.02.010 81 Feodorova, V. A. et al. Pleiotropic effects of the lpxM mutation in Yersinia pestis resulting in modification of the biosynthesis of major immunoreactive antigens. Vaccine 27, 2240-2250 (2009). https://doi.org:10.1016/j.vaccine.2009.02.020 82 Kim, S. H., Jia, W., Bishop, R. E. & Gyles, C. An msbB homologue carried in plasmid pO157 encodes an acyltransferase involved in lipid A biosynthesis in Escherichia coli O157:H7. Infect Immun 72, 1174-1180 (2004). https://doi.org:10.1128/IAI.72.2.1174-1180.2004 83 Mamat, U. et al. Endotoxin-free protein production—ClearColi™ technology. Nature Methods 10, 916-916 (2013). https://doi.org:10.1038/nmeth.f.367 84 Faivre, S., Chan, D., Salinas, R., Woynarowska, B. & Woynarowski, J. M. DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol 66, 225-237 (2003). https://doi.org:10.1016/s0006-2952(03)00260-0 85 Tesniere, A. et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29, 482-491 (2010). https://doi.org:10.1038/onc.2009.356 86 Fucikova, J. et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis 11, 1013 (2020). https://doi.org:10.1038/s41419-020-03221-2 87 Ma, Y. et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38, 729-741 (2013). https://doi.org:10.1016/j.immuni.2013.03.003 88 Schwechheimer, C., Kulp, A. & Kuehn, M. J. Modulation of bacterial outer membrane vesicle production by envelope structure and content. BMC Microbiol 14, 324 (2014). https://doi.org:10.1186/s12866-014-0324-1 89 Rastogi, I. et al. Role of B cells as antigen presenting cells. Front Immunol 13, 954936 (2022). https://doi.org:10.3389/fimmu.2022.954936 90 Patente, T. A. et al. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. Front Immunol 9, 3176 (2018). https://doi.org:10.3389/fimmu.2018.03176 91 Martin-Orozco, N., Isibasi, A. & Ortiz-Navarrete, V. Macrophages present exogenous antigens by class I major histocompatibility complex molecules via a secretory pathway as a consequence of interferon-gamma activation. Immunology 103, 41-48 (2001). https://doi.org:10.1046/j.0019-2805.2001.01226.x 92 Schetters, S. T. T. et al. Outer membrane vesicles engineered to express membrane-bound antigen program dendritic cells for cross-presentation to CD8(+) T cells. Acta Biomater 91, 248-257 (2019). https://doi.org:10.1016/j.actbio.2019.04.033 93 Xu, H. et al. The modulatory effects of lipopolysaccharide-stimulated B cells on differential T-cell polarization. Immunology 125, 218-228 (2008). https://doi.org:10.1111/j.1365-2567.2008.02832.x 94 Besser, M. J. et al. Modifying interleukin-2 concentrations during culture improves function of T cells for adoptive immunotherapy. Cytotherapy 11, 206-217 (2009). https://doi.org:10.1080/14653240802590391 95 Sudarsanam, H., Buhmann, R. & Henschler, R. Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions. Front Bioeng Biotechnol 10, 886637 (2022). https://doi.org:10.3389/fbioe.2022.886637 96 Kobayashi, S. D., Malachowa, N. & DeLeo, F. R. Neutrophils and Bacterial Immune Evasion. J Innate Immun 10, 432-441 (2018). https://doi.org:10.1159/000487756 97 Boutilier, A. J. & Elsawa, S. F. Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci 22 (2021). https://doi.org:10.3390/ijms22136995 98 Sun, F. et al. Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma. J Recept Signal Transduct Res 39, 208-214 (2019). https://doi.org:10.1080/10799893.2019.1655050 99 Goldberg, J. L. & Sondel, P. M. Enhancing Cancer Immunotherapy Via Activation of Innate Immunity. Semin Oncol 42, 562-572 (2015). https://doi.org:10.1053/j.seminoncol.2015.05.012 100 Nguyen, C. T. et al. Flagellin enhances tumor-specific CD8(+) T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model. Vaccine 31, 3879-3887 (2013). https://doi.org:10.1016/j.vaccine.2013.06.054 101 Rhee, S. H., Im, E. & Pothoulakis, C. Toll-like receptor 5 engagement modulates tumor development and growth in a mouse xenograft model of human colon cancer. Gastroenterology 135, 518-528 (2008). https://doi.org:10.1053/j.gastro.2008.04.022 102 Cai, Z. et al. Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth. Cancer Res 71, 2466-2475 (2011). https://doi.org:10.1158/0008-5472.CAN-10-1993 103 Sfondrini, L. et al. Antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer. J Immunol 176, 6624-6630 (2006). https://doi.org:10.4049/jimmunol.176.11.6624 104 Sonnenborn, U. & Schulze, J. The non-pathogenicEscherichia colistrain Nissle 1917 – features of a versatile probiotic. Microbial Ecology in Health and Disease 21, 122-158 (2009). https://doi.org:10.3109/08910600903444267 105 Kumar, S., Sunagar, R. & Gosselin, E. Bacterial Protein Toll-Like-Receptor Agonists: A Novel Perspective on Vaccine Adjuvants. Front Immunol 10, 1144 (2019). https://doi.org:10.3389/fimmu.2019.01144 106 Kim, J. Y. et al. Engineered bacterial outer membrane vesicles with enhanced functionality. J Mol Biol 380, 51-66 (2008). https://doi.org:10.1016/j.jmb.2008.03.076 107 Morrison, D. C. & Jacobs, D. M. Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides. Immunochemistry 13, 813-818 (1976). https://doi.org:10.1016/0019-2791(76)90181-6 108 Whitehead, B., Antennuci, F., Boysen, A. T. & Nejsum, P. Polymyxin B inhibits pro-inflammatory effects of E. coli outer membrane vesicles whilst increasing immune cell uptake and clearance. J Antibiot (Tokyo) 76, 360-364 (2023). https://doi.org:10.1038/s41429-023-00615-0 109 Wu, L. S. et al. LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis. Cancer Manag Res 12, 10397-10409 (2020). https://doi.org:10.2147/CMAR.S244374 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90325 | - |
| dc.description.abstract | 「外膜囊泡」是革蘭氏陰性細菌的外膜自然釋放出的胞外囊泡。此一種奈米顆粒大小的外膜囊泡含有豐富多樣的病原相關分子模式，其中包括格蘭氏陰細菌特有的內毒素「脂多醣」。近年來，許多研究利用外膜囊泡能夠引發先天性和適應性免疫反應的特性，將其廣泛應用在癌症免疫療法之領域。然而，外膜囊泡中作為誘導免疫反應與抑制腫瘤生長的關鍵成分，目前仍需更多詳細研究。在本篇研究中，我們系統地研究了脂多醣免疫原性對外膜囊泡抗腫瘤作用的影響。在我們的研究結果中顯示，脂多醣免疫原性的變化並不會影響外膜囊泡誘導抗原呈現細胞成熟的能力。然而，脂多醣免疫原性對外膜囊泡的抗腫瘤效應有著關鍵作用，而其中可能的原因為影響其招募白血球浸潤到腫瘤之中的能力有關。為了進一步增強對抗腫瘤的免疫反應，我們將外膜囊泡療法與化療藥物奧沙利寶結合使用，預期利用奧沙利寶誘導癌細胞引發免疫原性細胞死亡，並且協同外膜囊泡療法達到增強對抗腫瘤之免疫反應。此外我們嘗試將不同的類鐸受體激動劑表達在外膜囊泡上，預期能進一步增加其引發免疫反應對抗癌症之能力，儘管此策略在本次研究中未能產生預期的效果，但此種成功改造外膜囊泡的方式，仍然保有許多研究發展的可能性。總結，本篇研究揭示了脂多醣之免疫原性對於外膜囊泡建立免疫系統對抗癌症功效的重要性。 | zh_TW |
| dc.description.abstract | Outer membrane vesicles (OMVs) are nano-meter-sized exosomes naturally derived from the outer membrane of Gram-negative bacteria. They contain diverse pathogen-associated molecular patterns (PAMPs), with a particular enrichment of lipopolysaccharides (LPS). Recently, OMV-based applications have gained wide interest as cancer immunotherapy since they have been reported to provoke innate and adaptive immunity against tumors. However, the key component of OMVs that induces cancer immunity still remains largely unknown. In this study, we systemically investigated the impact of LPS immunogenicity on the anti-tumor effects of OMVs. Our results showed that variations in LPS immunogenicity did not affect the ability of OMVs to induce the maturation of antigen-presenting cells (APCs). However, we observed that the immunogenicity of LPS played a crucial role in the anti-tumor effects of OMVs, possibly by influencing the recruitment of tumor-infiltrating leukocytes. To further enhance the immune response against tumors, we combined the OMV-based therapy with the chemotherapeutic drug oxaliplatin, an inducer of immunogenic cell death (ICD), to synergistically boost immunity against the tumor. Moreover, we explored the possibility of enhancing OMV-based immune therapy by engineering additional Toll-like receptor agonists onto OMVs. Although this approach did not yield the desired outcome, the potential of engineered OMV-based therapy with other therapeutic proteins still holds great promise and warrants further investigation. Together, our findings shed light on the role of LPS immunogenicity in the recruitment of tumor-infiltrating leukocytes and its impact on the anti-tumor effects of OMVs. These insights contribute to a better understanding of OMVs as potential immunotherapeutic agents. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-26T16:16:33Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-09-26T16:16:33Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iii CONTENTS iv Chapter 1 Introduction 1 1.1 Outer membrane vesicles (OMVs) 1 1.2 The contribution of OMVs to bacterial survival and pathogenesis 2 1.3 Interactions between OMVs and Toll-like receptors 4 1.3.1 Toll-like receptors 4 1.3.2 PAMPs on OMVs 8 1.4 OMV biomedical applications 10 1.4.1 Bacterial vaccines 10 1.4.2 Vaccine adjuvants 11 1.4.3 Drug delivery vehicles 12 1.4.4 Cancer immunotherapy agents 14 1.5 Double-edge roles in OMVs cancer immunotherapy 15 1.5.1 Pro- and anti-tumor effects of TLR signaling 15 1.5.2 Pros and cons of LPS in cancer immune therapy 17 1.6 LPS-detoxified E. coli strains 18 1.6.1 Attenuated LPS derived from ∆mabB mutants 19 1.6.2 LPS precursor lipid IVa derived from endotoxin-free ClearColi strain 19 1.7 Chemotherapy drug: Oxaliplatin 19 Chapter 2 Materials and Methods 21 2.1 Plasmid construct 21 2.2 Cell line culture 21 2.3 Western blot 22 2.4 OMV purification 22 2.5 OMV characterization (particle size and zeta potential) 23 2.6 SEAP assay 23 2.7 Splenocytes isolation 24 2.8 Antigen-presenting cell maturation assay 24 2.9 Splenocytes proliferation assay 25 2.10 Mouse anti-tumor experiments 26 2.11 Cytometric Bead Array (CBA) assay 26 2.12 Tumor-infiltrating leukocytes (TILs) flow cytometry analysis 27 2.13 IVIS experiment 28 Chapter 3 Results 29 3.1 The characteristics of OMVs secreted from E. coli BL21(DE3) mutants 29 3.2 The OMVs induce the maturation of antigen-presenting cells 32 3.3 The OMVs stimulate T cell clonal expansion ex vivo 34 3.4 The LPS immunogenicity is crucial for anti-tumor effects of OMVs 38 3.5 The LPS immunogenicity of OMVs plays an important role on recruitment of tumor-infiltrating leukocytes 42 3.6 OMV distribution and tumor targeting efficiency in vivo 46 3.7 Approaches for enhancement of OMVs cancer immunotherapy with oxaliplatin 50 3.7.1 The anti-tumor effects of combination therapy with oxaliplatin and OMVs 51 3.7.2 The alteration of tumor-infiltrating leukocytes with oxaliplatin and ∆Lpp OMVs combination therapy 56 3.8 Approaches for anti-tumor effects improvement through engineered the TLR agonists on OMVs 59 3.8.1 Engineered BL21(DE3) ∆Lpp OMVs with flagellin 60 3.8.2 Engineered BL21(DE3) ∆Lpp ∆msbB OMVs carried with flagellin 63 3.8.3 Engineered ClearColi OMVs with flagellin 66 3.8.4 Engineered ClearColi OMVs with bacterial TLR4 agonists 70 Chapter 4 Discussion 73 REFERENCE 75 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 類鐸受體 | zh_TW |
| dc.subject | 奧沙利鉑 | zh_TW |
| dc.subject | 病原相關分子模式 | zh_TW |
| dc.subject | 腫瘤微環境 | zh_TW |
| dc.subject | 癌症免疫療法 | zh_TW |
| dc.subject | 脂多醣 | zh_TW |
| dc.subject | 細菌外膜囊泡 | zh_TW |
| dc.subject | Cancer immunotherapy | en |
| dc.subject | Oxaliplatin | en |
| dc.subject | Outer membrane vesicles | en |
| dc.subject | Tumor microenvironment | en |
| dc.subject | Pathogen-associated molecular patterns | en |
| dc.subject | toll-like receptor | en |
| dc.subject | Lipopolysaccharides | en |
| dc.title | 研究細菌外膜囊泡的抗腫瘤作用 | zh_TW |
| dc.title | Investigate the anti-tumor effects of bacterial outer membrane vesicles | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 張鑫;張永祺;胡哲銘 | zh_TW |
| dc.contributor.oralexamcommittee | Shin Chang;Yung-Chiy Chang;Che-Ming Hu | en |
| dc.subject.keyword | 細菌外膜囊泡,脂多醣,癌症免疫療法,腫瘤微環境,病原相關分子模式,類鐸受體,奧沙利鉑, | zh_TW |
| dc.subject.keyword | Outer membrane vesicles,Lipopolysaccharides,Cancer immunotherapy,Tumor microenvironment,Pathogen-associated molecular patterns,toll-like receptor,Oxaliplatin, | en |
| dc.relation.page | 82 | - |
| dc.identifier.doi | 10.6342/NTU202302088 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2023-07-27 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 微生物學研究所 | - |
| dc.date.embargo-lift | 2028-07-26 | - |
| 顯示於系所單位： | 微生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-111-2.pdf 未授權公開取用 | 5.2 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。