title: DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy.
abstract: We systematically investigated the impact of the relative maturation levels of dendritic cells (DCs) on their cell surface phenotype, expression of cytokines and chemokines/chemokine receptors (by DNA array and RNase protection analyses), biological activities, and abilities to induce tumor immunity. Mature DCs expressed significantly heightened levels of their antigen-presenting machinery (e.g., CD54, CD80, CD86) and numerous cytokines and chemokines/chemokine receptors (i.e., Flt-3L, G-CSF, IL-1alpha and -1beta, IL-6, IL-12, CCL-2, -3, -4, -5, -17, and -22, MIP-2, and CCR7) and were significantly better at inducing effector T cell responses in vitro. Furthermore, mice vaccinated with tumor peptide-pulsed mature DCs better survived challenge with a weakly immunogenic tumor (8 of 8 survivors) than did mice vaccinated with less mature (3 of 8 survived) or immature (0 of 8 survivors) DCs. Nevertheless, intermediate-maturity DCs expressed substantial levels of Flt-3L, IGF-1, IL-1alpha and -1beta, IL-6, CCL-2, -3, -4, -9/10, -17, and -22, MIP-2, osteopontin, CCR-1, -2, -5, and -7, and CXCR-4. Taken together, our data clearly underscore the critical nature of employing DCs of full maturity for DC-based antitumor vaccination strategies.
authors.affiliation: Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W0, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Dehm
authors.forename: K
authors.initials: K
authors.lastname: Bonham
authors.forename: H
authors.initials: H
authors.lastname: Kamencic
authors.forename: B
authors.initials: B
authors.lastname: Juurlink
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J R
authors.initials: JR
authors.lastname: Gordon
authors.forename: J
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000032:analysis; D019496:Cancer Vaccines; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000943:Antigens, Differentiation; D019496:Cancer Vaccines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger