Transduction of dendritic cells with Bcl-x(L) increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice

We have shown that prostate cancer (PCa) causes apoptosis of dendritic cell s (DC), which might block the development of specific antitumor immune resp onses. Analysis of murine prostatic carcinoma tissues revealed the signific ant decrease in intratumoral DC number during tumor progression. We demonst rated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-x(L). Next, we ev aluated the resistance to tumor-induced apoptosis and the antitumor efficie ncy of genetically engineered DC overexpressing Bcl-x(L). DC were transduce d with an adenoviral vector encoding the murine Bcl-x(L) gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice w ith Bcl-x(L)-transduced DC resulted in significant inhibition of tumor grow th compared with the administration of nontransduced DC. Thus, our data sug gest that the protection of DC from PCa-induced apoptosis might significant ly increase the efficacy of DC-based therapies in cancer even in the absenc e of available tumor-specific Ags.