Conclusion
cdG/Mix triggered ICD in various cancer cells and reversed the Tex systemically in tumor-burden mice, which would be a promising alternative strategy for cancer immunotherapy.
Methods
The optimal composition of Mix for cDNs encapsulation was explored with RAW-Lucia ISG cells. The physicochemical properties of resulted nanoparticles were characterized. To validate the anti-tumor immunity of cDNs/Mix both in vitro and in vivo, immunogenic cell death (ICD) related markers and tumor inhibition efficacy were evaluated in cancer cells and tumor models, respectively. The mechanism by which cdG/Mix exerted the antitumor effects was explored by flow cytometric analysis and in vivo depletion.
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.