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Lipid-Glycoadjuvant@AuNPs Inhibits Tumor Gowth and Regulates Tumor Microenvironments by Tumor-Specific CTL-Ferived IFNγ


 Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. However, clinical benefits of CpG based tumor vaccine were limited primarily due to the poor targeting to lymph nodes. Here we developed a lipid-glycoadjuvant@AuNPs (LCpG) by covalent conjugation of CpG with lipid-glycopolymers, which could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen–specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, inhibited Treg differentiation and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. Together, our results demonstrated that LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.