The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles’ elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.

个性化癌症免疫治疗的成功取决于树突状细胞和巨噬细胞的初始肿瘤抗原呈递。肿瘤源性细胞外囊泡（TEV）含有丰富的肿瘤抗原分子。然而，TEV 表面上存在的抗吞噬信号，例如分化簇 47 (CD47)，会导致相同的树突状细胞和巨噬细胞的逃避。在这里，我们证明氧化铁氢氧化物纳米复合材料可以成功掩盖 TEV 表面并解锁吞噬作用，而不影响细胞外囊泡引发的免疫目标。内化后，掩模在溶酶体中崩解，释放肿瘤抗原货物。在动物模型中，这会触发抗原呈递并促进树突状细胞活化和成熟以及巨噬细胞重编程，从而导致肿瘤体积和转移急剧减少，并且在人类恶性胸腔积液临床样本中也是如此。这种简单的掩蔽策略消除了临床样本中普遍存在的抗吞噬作用块，并且可以普遍应用于所有患者特异性 TEV，作为增强免疫治疗的肿瘤抗原剂。