title: Adjuvant effect of a natural TLR4 ligand on dendritic cell-based cancer immunotherapy.
abstract: The clinical efficacy of dendritic cell (DC) vaccine in cancer patients has been unsatisfactory due, at least in part, to the deficiency of maturation and impaired migration of ex vivo generated DCs to the draining lymph nodes. To solve this problem, we used angelan, a natural TLR4 ligand, to enhance the maturation and migration of DCs. Angelan increased the expression of MHC-I/II, CD80, and CD86, DC maturation markers, through the NF-κB pathway. This compound also increased CCR7 expression in DCs through NF-κB and p38 pathway and enhanced their migration against CCL19, which is a key chemokine that guides DCs into lymph nodes. We also showed that angelan enhanced in vivo DC homing from tissues to draining lymph nodes. When treated to DCs in vitro and vivo, angelan increased antitumor activity of DCs in B16F10 syngeneic tumor model. Taken together, the present data suggest that a natural TLR4 ligand might be helpful for overcoming the disadvantages of DC-based cancer therapy, such as impaired maturation and poor migration in cancer patients.
authors.affiliation: College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Yeon Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hwa Sun
authors.initials: HS
authors.lastname: Ryu
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D054415:Chemokine CCL19 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D011134:Polysaccharides / Q000494:pharmacology*; D054400:Receptors, CCR7 / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; C497965:Cd86 protein, mouse; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016328:NF-kappa B; D011134:Polysaccharides; D054400:Receptors, CCR7; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C515883:angelan; D020928:Mitogen-Activated Protein Kinases