ReferenceID 3787
Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
J Biomed Sci
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-depol
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Record Fields
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- Reference Id
- 3787
- Evidence Id
- 20377
- Core Evidence Id
- 20377
- Source Reference Id
- 858
- Herb2 Reference Id
- HBREF001473
- Subject Paper Key
- HBIN021260_21689407
- Pubmed Id
- 21689407
- Doi
- 10.1186/1423-0127-18-44
- Paper Title
- Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
- Paper Abstract
- 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.
- Journal
- J Biomed Sci
- Publish Year
- 2011
- Experiment Subject
- cells: tumor cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
- Bilingual Status
- semi_complete