Recently, the possibility of BTLA as a potential therapeutic target in cancer immunotherapy has been established in vivo, wherein human melanoma tumor antigen-specific effector CD8+ T cells expressing high levels of BTLA were downregulated with a vaccine formulated using CpG oligodeoxynucleotides, a toll-like receptor 9 (TLR9) agonist that triggers innate immunity, thereby proving that inhibition of BTLA may partially reverse the function of human CD8+ cancer-specific T cells (Derr et al., 2010; Paulos and June, 2010). Here, TLR9 is linked to cancer.