Numerical and functional assessment of blood dendritic cells in prostate cancer patients.
BACKGROUND
Prostate cancer is one of the leading causes of cancer deaths in males and there are currently no effective treatments available for metastatic disease. Although recent clinical trials using dendritic cell (DC) based immunotherapy treatments have demonstrated safety, immunological responses, and some clinical efficacy, better vaccine delivery strategies need to be developed. We have undertaken the first detailed analysis of blood DC (BDC) subsets and their function in prostate cancer patients, with a view to utilizing immunoselected BDC for immunotherapy.


METHODS
We enumerated the CD11c+CD1c+, CD11c+CD16+, and CD11c-CD123+ BDC subsets in whole blood of prostate cancer patients using a single platform TruCOUNT assay. These subsets were identified and purified using flow cytometry and immunomagnetic selection, and their functional capacity analyzed by costimulatory molecule expression, cytokine secretion, and antigen presenting ability.


RESULTS
There were no significant differences in the number or composition of these subsets compared to healthy donors and these cells could be purified with equal efficiency from both groups. The prostate cancer patients BDC had similar levels of key costimulatory molecules and cytokine expression profiles, compared to healthy donors, and these were upregulated to the same extent, in response to exogenous stimuli. BDC from both groups were capable of eliciting allogeneic proliferative responses and inducing autologous CD4+ responses to naïve and recall antigens, and antigen-specific CD8+ responses to influenza matrix protein and prostate specific antigen.


CONCLUSIONS
These results indicate that an immunoselected CD1c+ BDC preparation could provide a suitable vaccine delivery vehicle for future prostate cancer immunotherapy trials.
Wilkinson
Ray
R
Mater Medical Research Institute, Aubigny Place, Raymond Terrace, South Brisbane, Queensland, Australia.
Kassianos
Andrew J
AJ
Swindle
Peter
P
Hart
Derek N J
DN
Radford
Kristen J
KJ
D000368:Aged; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002452:Cell Count; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II