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A Bacterial Flagellin in Combination With Proinflammatory Cytokines Activates Human Monocyte-derived Dendritic Cells to Generate Cytotoxic T Lymphocytes Having Increased Homing Signals to Cancer

Authors :
Soo Young Kim
Hyun-Ju Lee
Joon Haeng Rhee
Sang Chul Lim
Cheol Yi Hong
Shee Eun Lee
Je-Jung Lee
Source :
Journal of Immunotherapy. 37:16-25
Publication Year :
2014
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2014.

Abstract

Flagellin, the cognate ligand for toll-like receptor 5, has potent adjuvant activity in various vaccines. However, its efficacy in generating dendritic cells (DCs) remains contentious. This study assessed how efficaciously Vibrio vulnificus FlaB (v-FlaB) could be used in generating a potent DC to induce antigen-specific cytotoxic T lymphocytes (CTLs). Mature DCs (mDCs) induced by the combination of v-FlaB/TNFα/IFNα were significantly more potent in inducing specific anticancer immune responses compared with the standard DCs that were maturated by the conventional cytokine cocktail of TNFα/IL-1β/IL-6/PGE(2). The potent mDCs produced a higher level of interleukin (IL)-12p70 and polarized naive CD4(+) T cells more towards Th1-type cells, markedly increased antigen-specific CD8(+) T-cell number and significantly enhanced the induction of lytic enzymes in antigen-specific CD8(+) CTLs and sensitized CD3(+) T cells to produce higher number of interferon (IFN)γ-secreting cells. As a result, the mDCs produced more potent antigen-specific CTLs against the MART-1 and expressed higher levels of homing receptors CCR5 and CXCR3. More importantly, the v-FlaB/TNFα/IFNα-DCs generated from melanoma patients produced strong autologous CTLs with efficient cytotoxic activities. In conclusion, v-FlaB combined with tumor necrosis factor (TNF)α and IFNα can generate potent DCs which produce functionally active CTLs and that may have potential as a potent cancer vaccine.

Details

ISSN :
15249557
Volume :
37
Database :
OpenAIRE
Journal :
Journal of Immunotherapy
Accession number :
edsair.doi.dedup.....6ed5600a87d610bd912861eb92b596f3
Full Text :
https://doi.org/10.1097/cji.0000000000000008