Phenotypic and functional characterization of mature dendritic cells from pediatric cancer patients.
BACKGROUND
Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system. Clinical trials have demonstrated that mature DCs loaded with tumor-associated antigens can induce tumor-specific immune responses. Theoretically, pediatric patients are excellent candidates for immunotherapy since their immune system is more potent compared to adults. We studied whether sufficient amounts of mature monocyte-derived DCs can be cultured from peripheral blood of pediatric cancer patients.


METHODS
DCs from 15 pediatric patients with an untreated primary tumor were cultured from monocytes and matured with clinical grade cytokines. Phenotype and function were tested with flow cytometry, mixed lymphocyte reaction (MLR), and an in vitro migration assay. DCs of children with a solid tumor were compared with monocyte-derived DCs from age-related non-malignant controls.


RESULTS
Ex vivo-generated monocyte-derived DCs from pediatric patients can be generated in numbers sufficient for DC vaccination trials. Upon cytokine stimulation the DCs highly upregulate the expression of the maturation markers CD80, CD83, and CD86. The mature DCs are six times more potent in inducing T cell proliferation compared to immature DCs. Furthermore, mature DCs, but not immature DCs, express the chemokine receptor CCR7 and have the capacity to migrate in vitro.


CONCLUSIONS
These data indicate that mature DCs can be generated ex vivo to further optimize DC-vaccination trials in pediatric cancer patients.
Jacobs
Joannes F M
JF
Department of Pediatric Hemato-Oncology, Nijmegen Centre of Molecular Life Sciences, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Hoogerbrugge
Peter M
PM
de Rakt
Mandy W M M van
MW
Aarntzen
Erik H J G
EH
Figdor
Carl G
CG
Adema
Gosse J
GJ
de Vries
I Jolanda M
IJ
D000293:Adolescent; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines