Priming of CD8⁺ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1⁺ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14⁺ CD169⁺ monocytes and Axl⁺ CD169⁺ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169⁺ moDCs and Axl⁺ CD169⁺ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8⁺ T cells. Finally, Axl⁺ CD169⁺ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169⁺ DCs to drive antitumor T cell responses.

树突状细胞 (DC)启动 CD8 ⁺ T 细胞对于产生有效的抗肿瘤免疫反应至关重要。在这里，我们描述了一种脂质体疫苗载体，它使用神经节苷脂作为靶向配体将肿瘤抗原递送至人类 CD169/Siglec-1 ⁺抗原呈递细胞。神经节苷脂脂质体特异性结合 CD169，并以 CD169 依赖性方式被体外产生的单核细胞衍生的 DC (moDC) 和巨噬细胞以及离体分离的脾巨噬细胞内化。在血液中，高维还原分析表明神经节苷脂脂质体特异性靶向CD14 ⁺ CD169 ⁺单核细胞和Axl ⁺ CD169 ⁺ DC。肿瘤抗原和Toll样受体配体的脂质体共递送至CD169 ⁺ moDC和Axl ⁺ CD169 ⁺ DC，导致细胞因子的产生以及肿瘤抗原特异性CD8 ⁺ T细胞的强劲交叉呈递和激活。最后，Axl ⁺ CD169 ⁺ DC 存在于癌症患者体内并有效捕获神经节苷脂脂质体。我们的研究结果证明了一个针对 CD169 ⁺ DC 的纳米疫苗平台可驱动抗肿瘤 T 细胞反应。