TLR9 signaling promotes tumor progression of human lung cancer cell in vivo.

Toll like receptor 9 (TLR9) was identified mainly in cells of the immune system, and CpG oligonucleotides (CpG ODN), which induces signaling through TLR9, are currently under investigation as adjuvants in clinical therapies against cancer. However, accumulating data suggested that functional TLR9 was also expressed in tumor cells and the effects of TLR9 signaling on the progression of tumor cells remain undefined. Our previous study demonstrated that the TLR9 signaling could significantly enhance the metastatic potential of human lung cancer cells in vitro. Here we carefully evaluated the direct effect of TLR9 signaling on tumor progression of human lung cancer cells in vitro and in vivo. We observed that TLR9 agonist CpG ODN could robustly enhance the tumor progression of 95D cells which expressed high level of TLR9 in nude mice. Furthermore, the CpG ODN could effectively induce the proliferation and IL-10 secretion of 95D cells in vitro. Finally, we demonstrated that CpG ODN could significantly elevate the tumor progression of TLR9 modifying 95C cells in vitro and in vivo, which could be dramatically abrogated by the inhibitory CpG ODN. Our findings indicated that the TLR9 signaling could promote the tumor progression of human tumor cells, which might provide novel insight into the implications for CpG based anti-tumor therapies.