TLR9 and neoplasm: To overcome this challenge, we developed CpG7909 (a TLR9 agonist) lipoplex using a cationic lipid formulation, which exhibited preferential accumulation in tumors and spleen following systemic administration, Combination immunotherapy with an anti-PD1 antibody and CpG7909 lipoplex significantly promoted the infiltration of CD8+ T cells (> twofold) into the TME of the CT26 tumor animal model and effectively inhibited both deep-seated colorectal and metastatic lung tumors.