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Title:
Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines | Journal of Biomedical Science
Description:
Background Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. Methods In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. Results The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Conclusions Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.
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Keywords {π}
cells, cell, tumor, pubmed, dcs, article, google, scholar, vaccines, cas, cancer, dendritic, mice, expression, figure, group, test, colchicine, death, immunogenic, pulsed, melanoma, cmq, mdas, immunity, control, agents, effect, tcls, treated, dcbased, culture, gmcsf, ilp, induce, shown, vaccine, antitumor, fmq, versus, specific, survival, tclcmq, immunol, proliferation, production, hours, injection, activity, treatment,
Topics {βοΈ}
granulocyte/macrophage colony-stimulating factor dendritic-cell-based functional screening cytokine-regulated anti-tumor immunity microtubule-mediated nf-kappab activation tcl-pulsed dc-based vaccines sheng-chu kuo dcs [anti-cd40-fluorescein isothiocyanate dendritic cell-derived exosomes open access article tcl-dx-pulsed dc vaccine article download pdf jin-bin wu dendritic cells-based vaccines specific microtubule-depolymerizing agents cell-based cancer vaccines allogeneic t-cell reaction ifn-{alpha}2a therapy dc-based vaccines pulsed dc-based cancer vaccines dc-based vaccine pulsed developing anti-cancer vaccines gibco/brl life technologies tcl-dmso-pulsed dcs showed hrp-labeled anti-mouse tnf-alpha signaling pathway national yang-ming university tcl-pulsed dc vaccines promoting anti-tumor immunity promote antigen-cross presentation promote antigen cross-presentation high-mobility group box-1 confer anti-cancer activity biomedical science aims il-4-mediated fine tuning subsequent t-cell proliferation confer anti-tumor activity tumour immunotherapy antigen cross-presentation activity fmq phytocompound-derived chemicals enhance tumor-specific immunity hrp-conjugated secondary antibody specific pathogen-free conditions enhance anti-tumor activity antigen-specific adaptive immunity shikonin-enhanced cell immunogenicity cd8+ t-cell responses freeze-thaw-sonicated cycle tumor-bearing mice areas ning-sun yang kaplan-meier survival curves
Questions {β}
- Viaud S, Thery C, Ploix S, Tursz T, Lapierre V, Lantz O, Zitvogel L, Chaput N: Dendritic cell-derived exosomes for cancer immunotherapy: what's next?
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headline:Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
description:Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.
datePublished:2011-06-20T00:00:00Z
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immunogenic cell death
colchicine
2-phenyl-4-quinolone
dendritic cells
cancer vaccine
Biomedicine
general
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headline:Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
description:Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.
datePublished:2011-06-20T00:00:00Z
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immunogenic cell death
colchicine
2-phenyl-4-quinolone
dendritic cells
cancer vaccine
Biomedicine
general
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