Although immune checkpoint inhibitors have significantly improved clinical outcomes in various malignant cancers, only a small proportion of patients reap benefits, likely due to the low number of T cells and high number of immunosuppressive cells in the tumor microenvironment (TME) of patients with advanced disease. We developed a cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) and analyzed its therapeutic effect alone or in combination with immune checkpoint inhibitors, on antitumor immune responses and the reprogramming of suppressive immune cells in the TME. NE (R848) demonstrated robust local and systemic antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, inducing tumor-specific T cell activation and mitigating T cell exhaustion. Combination with anti-PD-1 antibodies showed synergistic effects with respect to therapeutic efficacy and survival rate. Thus, NE (R848)-based cancer vaccines could prevent tumor recurrence and prolong survival by activating antitumor immunity and reprogramming immunosuppression.

尽管免疫检查点抑制剂显着改善了各种恶性肿瘤的临床结果，但只有一小部分患者受益，这可能是由于晚期疾病患者的肿瘤微环境 (TME) 中 T 细胞数量少而免疫抑制细胞数量多. 我们开发了一种以载有 TLR7/8 激动剂 (R848) 的纳米乳 (NE) 为佐剂的癌症疫苗，并分析了其单独或与免疫检查点抑制剂联合使用对 TME 中抗肿瘤免疫反应和抑制性免疫细胞重编程的治疗效果。NE (R848) 在皮下和原位小鼠肺癌模型中表现出强大的局部和全身抗肿瘤免疫反应，诱导肿瘤特异性 T 细胞活化并减轻 T 细胞耗竭。与抗 PD-1 抗体的组合在治疗效果和存活率方面显示出协同作用。因此，基于 NE (R848) 的癌症疫苗可以通过激活抗肿瘤免疫和重新编程免疫抑制来预防肿瘤复发并延长生存期。