Functional TLR-9 expression, regulation and clinical significance in GBM patients

3557 Toll-like receptor-9 (TLR-9) is a pattern recognition receptor, which plays very important role in innate immunity. Placyticoid dendritic cells, B cells, langerhans and NK cells express TLR-9. Unmethylated CpG from bacterials can activate TLR-9. However, TLR-9 expression in tumor cells and its function is still unclear. We found that TLR-9 mRNA was expressed in 65% glioblastoma multiforme (GBM) cultured tumor cells by RT-PCR analysis. The protein expression of TLR-9 in tumor cells and tissue was confirmed by flow cytometry and immunofluorence analysis. Different type of commercial available CpG ODN was tested the function of TLR-9 in GBM. We found that class A CpG increased TRAIL expression and inhibited GBM cells proliferation while class B CpG stimulated IL-6 expression and increased GBM cells proliferation. Receptor tyrosine kinase inhibitor (RTK) geldanamycin and cyclooxygenase-2 (COX-2) inhibitor could significantly increased TLR-9 expression, however, TNF-α treatment significantly decreased TLR-9 expression. Finally, we found that TLR-9 positive GBM patients presented significantly longer survival than those of TLR-9 negative GBM patients. This study suggested that TLR-9 could be a useful prognosis biomarker in GBM patients and class A CpG ODN may be a promising reagent for cancer immunotherapy.