Effective antigen cross-presentation by prostate cancer patients' dendritic cells: implications for prostate cancer immunotherapy.
Despite the potency with which dendritic cells (DCs) are able to utilize the exogenous MHC I antigen cross-presentation pathway to cross-present antigen for the activation of killer T cells in model systems, concern about defects in immune function in cancer patients has led to uncertainty regarding whether immune cells derived from patients can effectively be used to generate tumor vaccines. We have undertaken a careful analysis of the potency of using DCs obtained from prostate cancer patients to cross-present antigen derived from human prostate tumor cells for the activation of antigen-specific T cells. Such DCs can be matured ex vivo into functionally active cells and are capable of cross-presenting influenza antigen derived from internalized apoptotic prostate tumor cells. Importantly, we demonstrate effective stimulation of both CD4+ and CD8+ T cells, as evident by production of IFN-gamma, and the ability of CD8+ T cells to differentiate into effector CTLs. These results, defining conditions in which prostate cancer patient DCs can efficiently utilize the cross-presentation pathway and in which apoptotic tumor can serve as a source of antigen for DCs to activate T cells, demonstrate that this system warrants clinical study as a potential immunotherapy.
Howard Hughes Medical Institute, and Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY 10021, USA.
D E
DE
Orange
M
M
Jegathesan
N E
NE
Blachère
M O
MO
Frank
H I
HI
Scher
M L
ML
Albert
R B
RB
Darnell
D000951:Antigens, Neoplasm; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm