title: 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.
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.
authors: *Clinical Vaccine R&D Center, Chonnam National University ¶Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo Departments of †Hematology-Oncology ‡Microbiology §Pharmacology and Dental Therapeutics ∥Otolaryngology-Head and Neck Surgery, Chonnam National University, Gwangju, Republic of Korea.
authors: Cheol Yi
authors: CY
authors: Hong
authors: Soo Young
authors: SY
authors: Kim
authors: Hyun-Ju
authors: HJ
authors: Lee
authors: Shee Eun
authors: SE
authors: Lee
authors: Sang Chul
authors: SC
authors: Lim
authors: Joon Haeng
authors: JH
authors: Rhee
authors: Je-Jung
authors: JJ
authors: Lee
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D054400:Receptors, CCR7 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008024:Ligands; D054400:Receptors, CCR7; D005408:Flagellin; D018664:Interleukin-12