DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy.
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.
Chen
Z
Z
Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W0, Canada.
Dehm
S
S
Bonham
K
K
Kamencic
H
H
Juurlink
B
B
Zhang
X
X
Gordon
J R
JR
Xiang
J
J
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
D000943:Antigens, Differentiation; D019496:Cancer Vaccines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger