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The future of CpG immunotherapy in cancer.

Progress of ‘free’ CpG DNA oligonucleotides containing unmethylated deoxycytidylyl-deoxyguanosine dinucleotides are commonly referred to as CpGs. The unmethylated CG sequence is characteristic of bacterial DNA. CpGs stimulate mammalian immune cells through recognition by Toll-like receptor (TLR)9 [1]. Unlike many other TLRs, TLR9 is not found on the surface of cells, but is initially localized in the endoplasmic reticulum and is then found colocalized with CpGs in lysosomes following stimulation. TLR9 stimulation by CpGs initiates the production of cytokines and can lead to both the destruction of nearby antigens and the induction of memory T cells against those antigens. This cascade has been exploited to use CpGs as potent immunostimulatory agents for both innate and specific immunity. In particular, CpGs stabilized with phosphorothioate backbones have demonstrated excellent activity in experimental models against allergies, viral infections and cancer. This editorial will focus on the use of CpGs in cancer immunotherapy.