Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer.
Dendritic cells (DCs) are antigen-presenting cells specialized for the induction of the primary T-cell response. Tumor immunotherapy using DCs loaded with tumor antigens is under way for patients with several types of advanced malignancies. In this study, DC-like cells (Mo-DCs) were generated from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor and interleukin-4. The antigen-presenting abilities, including capture of apoptotic tumor cells, IL-12 secretion, expression of antigen-presentation-related molecules (HLA-ABC, HLA-DR, and CD80), and mixed leukocyte reaction, of Mo-DCs from 37 patients with advanced cancer (pMo-DCs) were compared to those of 20 healthy volunteers (hMo-DCs). Seven days after the initial culture, no significant difference was found in either the number or the size of Mo-DC-forming colonies between the two groups. However, most of the antigen-presenting abilities of pMo-DCs were weaker than those of hMo-DCs on day 7. On day 14, both number and size of colonies were significantly decreased in pMo-DCs but not in hMo-DCs. Interestingly, the antigen-presenting abilities of the remaining pMo-DCs gradually strengthened with time and by day 14 no significant difference was observed between pMo-DCs and hMo-DCs. These results indicate that pMo-DCs contain dysfunctional and short-lived Mo-DC subsets.
Onishi
Hideya
H
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Morisaki
Takashi
T
Baba
Eishi
E
Kuga
Hirotaka
H
Kuroki
Hideo
H
Matsumoto
Kotaro
K
Tanaka
Masao
M
Katano
Mitsuo
M
D000368:Aged; D017951:Antigen Presentation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009369:Neoplasms / Q000628:therapy*; D013997:Time Factors
D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor