Advanced neuroblastoma impairs dendritic cell function in adoptive immunotherapy.
OBJECTIVE
The authors previously described the complete regression of established neuroblastoma (NB) by the adoptive transfer of syngeneic interleukin-12 transduced dendritic cells (DC) from naive mice. However, some malignancies, like NB, abrogate DC immunostimulation. The authors hypothesize that IL-12 transduction of DC from NB-bearing mice will have the same antitumor properties.


METHODS
A/J mice (n = 32) with established NB received peritumoral injection of 1 x 10(6) DC (DC, IL-12 DC, day 7 IL-12 DC or day 14 IL-12 DC) on day 7. Tumor growth, phenotype, and ability to induce NK and T cell activity were measured.


RESULTS
Vaccination with naive admIL-12 DC resulted in 100% tumor regression and prolonged survival. Transduced DC induced only partial responses in 75% (day 7) and 25% (day 14) of animals. No differences in phenotype or effector cell activation were noted between admIL-12DC in tumor-bearing or naive mice.


CONCLUSIONS
IL-12 DC from tumor-bearing animals have a decreased ability to induce antitumor activity against established murine NB. This decreased capacity appears to be related to the duration of exposure to tumor because day 14 transduced DC had less of an effect than day 7 DC, despite similar phenotypes and ability to activate immune effector cells.
Redlinger
Richard E
RE
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mailliard
Robbie B
RB
Barksdale
Edward M
EM
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D018664:Interleukin-12