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

作者：Hong Cheol Yi; Kim Soo Young; Lee Hyun Ju; Lee Shee Eun; Lim Sang Chul; Rhee Joon Haeng; Lee Je Jung^*

来源：Journal of Immunotherapy, 2014, 37(1): 16-25.

DOI：10.1097/CJI.0000000000000008

• dendritic cells
• v-FlaB
• Vibrio vulnificus
• proinflammatory cytokines

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/TNF/IFN were significantly more potent in inducing specific anticancer immune responses compared with the standard DCs that were maturated by the conventional cytokine cocktail of TNF/IL-1/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)-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/TNF/IFN-DCs generated from melanoma patients produced strong autologous CTLs with efficient cytotoxic activities. In conclusion, v-FlaB combined with tumor necrosis factor (TNF) and IFN can generate potent DCs which produce functionally active CTLs and that may have potential as a potent cancer vaccine.

• 出版日期2014-1