Evaluation of a dysfunctional and short-lived subset of monocyte-derived dendritic cells from cancer patients.
Monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood monocytes of 12 healthy volunteers (hMo-DCs) and 11 patients (pMo-DCs) with malignancies by culture for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4. In this study, we focused on the cytogram pattern by FACS analysis. A gate (R1) was set up by which more than 95% of hMo-DCs were contained. Mo-DCs having lower side scatter than the R1 (R2) comprised 4.5% of hMo-DCs and 24.2% of pMo-DCs. Expressions of antigen presentation-related molecules and phagocytic ability in the R2 of pMo-DCs were lower than those in the R1 population. The R2, but not R1, in pMo-DCs decreased in number between days 7 and 14, and expression levels of antigen presentation-related molecules in the living pMo-DCs on day 14 increased. The 11 patients received dendritic cell vaccine therapy with autologous, tumor-pulsed mature Mo-DCs (day 7). The low R2 group (R2 < or = 10%, 3 patients) had a significantly higher positive delayed-type hypersensitivity reaction against autologous tumor-pulsed Mo-DCs than that of the high R2 group (R2 > 10%, 8 patients) (p<0.001). These results indicate that the R2 of pMo-DCs may be a dysfunctional and short-lived subset.
Onishi
Hideya
H
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Morisaki
Takashi
T
Kuroki
Hideo
H
Matsumoto
Kotaro
K
Baba
Eishi
E
Kuga
Hirotaka
H
Tanaka
Masao
M
Katano
Mitsuo
M
D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D004067:Digestive System Neoplasms / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged
D018122:B7-1 Antigen; D039521:CD11c Antigen; D019496:Cancer Vaccines; D006684:HLA-DR Antigens