Dendritic Cells Pulsed with Irradiated Prostate Tumor Cells Express CC Receptor-7 and Its Ligands and Initiate a Tumor Specific Immune Response

Abstract

AIM: Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune response in cancer. This study is to address whether irradiated prostate cancer cells have the capability to induce DCs to respond against a tumor. METHODS: A highly tumorigenic mouse prostate tumor cell line RM-1 was subjected to γ-irradiation and tested for induction of apoptosis by exploiting DNA analysis and Hoechst staining. Various in vitro experiments were carried out to ascertain whether the irradiated tumor cells could activate DCs, and whether the DCs pulsed with irradiated tumor cells could stimulate splenocytes obtained from naive C57BL/6J animals. RESULTS: Irradiation (10 and 60 Gy) caused apoptosis in RM-1 cells and DCs were able to preferentially take up irradiated RM-1 cells. The irradiated RM-1 cells were immunostimulatory even at comparatively low stimulator/responder ratios as determined by co-culture experiments. By contrast, non-irradiated tumor cells were unable to stimulate comparable response. Moreover, the DCs pulsed with irradiated RM-1 cells could express high amounts of CCR-7 and its ligands, CCL-19 and CCL-21. The splenocytes when stimulated with these activated DCs showed significant cytotoxic activity against fresh RM-1 cells, and they also secreted high levels of interferon-γ and interleukin-12. CONCLUSION: This is the first demonstration that irradiated prostate tumor cells can activate DCs and these DCs express CCR-7 and its ligands, CCL-19 and CCL-21. The activated DCs are further capable of stimulating splenocytes of naive animals. These results have potential implications in designing effective DC-based immunotherapeutic strategy for prostate cancer treatment.