Results: Based on our developed and optimized delivery system, neutral cytidinyl lipid DNCA/cationic lipid CLD (Mix), cdG (500 nM in vitro, 1-10 μg in vivo)/Mix not only more potently stimulated production of IFNβ and related cytokines including CXCL9 and CXCL10, promoted ICD, led to NK and CD8+ T cell activation, inhibited tumor growth in both EO771 and B16F10 models and increased their survival rate (~43%), but also obviously reversed the T cell exhaustion (Tex) in tumor, meanwhile down regulated the mRNA expression of Tox and Nr4a, which are key regulators of Tex. This evidence concerns the gene CD8A and neoplasm.