'Survival gene' Bcl-xl potentiates DNA-raised antitumor immunity.
T-cell priming is strongly affected by the longevity of antigen-bearing dendritic cells (DCs), which are typically short-lived in lymphoid tissues. 'Survival gene' Bcl-xl is critical for the lifespan of DCs in vivo. Here, we showed that in vivo coadministration of Bcl-xl under control of the DC-specific promoter (CD11c-Bcl-xl) and TRP2hsp70 DNA prolonged T-cell stimulation by DCs and augmented TRP2-specific-IFN-gamma-producing CD8+ T-cell responses. Consistent with these findings, enhanced protection and significant therapeutic immunity to B16 melanoma was generated by this coimmunization strategy, which also augmented therapeutic immunity to GL-26 tumor. In this B16 melanoma model, results from animal experiments with depletion of immune cells indicate that CD8+ T cells and NK cells are important in the antitumor immunity induced by this coimmunization strategy. These observations suggest that 'survival gene' Bcl-xl potentiates the magnitude of antigen-specific-CD8+ T-cell responses and the efficacy of antitumor immunity induced by DNA vaccine, and is relevant for the design of in vivo targeted DC-based vaccine strategies to improve immunity against cancer.
Kim
J H
JH
Department of Dermatology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Chen
J
J
Majumder
N
N
Lin
H
H
Falo
L D
LD
You
Z
Z
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens; D039521:CD11c Antigen / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000276:immunology / Q000628:therapy; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage*; D051020:bcl-X Protein / Q000235:genetics*
D000951:Antigens, Neoplasm; D001324:Autoantigens; D039521:CD11c Antigen; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D019444:Vaccines, DNA; D051020:bcl-X Protein; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase