Transduction of dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice.
We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells (DC), which might block the development of specific antitumor immune responses. Analysis of murine prostatic carcinoma tissues revealed the significant decrease in intratumoral DC number during tumor progression. We demonstrated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-xL. Next, we evaluated the resistance to tumor-induced apoptosis and the antitumor efficiency of genetically engineered DC overexpressing Bcl-xL. DC were transduced with an adenoviral vector encoding the murine Bcl-xL gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice with Bcl-xL-transduced DC resulted in significant inhibition of tumor growth compared with the administration of nontransduced DC. Thus, our data suggest that the protection of DC from PCa-induced apoptosis might significantly increase the efficacy of DC-based therapies in cancer even in the absence of available tumor-specific Ags.
Departments of Urology, Surgery, and Biochemistry and Molecular Genetics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
G
G
Pirtskhalaishvili
G V
GV
Shurin
A
A
Gambotto
C
C
Esche
M
M
Wahl
Z R
ZR
Yurkovetsky
P D
PD
Robbins
M R
MR
Shurin
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology*; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D018450:Disease Progression; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006131:Growth Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D018664:Interleukin-12