PDF(Pubmed)
Abstract：
Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNPcancer cell@MVDC). This approach transforms immune-cold tumors, increases migratory DCs, activates T cells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. In vivo imaging reveals superior cNPcancer cell@MVDC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments.
摘要：
低迁移树突状细胞（DC）水平对癌症免疫监视构成挑战，然而,它们对肿瘤免疫状态和免疫治疗反应的影响尚不清楚.我们提供了临床证据，将降低的迁移DC水平与免疫冷肿瘤状态联系起来，导致患者预后不佳。为了解决这个问题，我们开发了一种基于自体DC的纳米接种策略,使用患者来源的类器官或癌细胞裂解物脉冲阳离子纳米粒子(cNPs)加载免疫原性DC来源的微泡(cNPancercell@MVDC).这种方法转化了免疫冷肿瘤，增加迁徙DC，激活T细胞和自然杀伤细胞,减少肿瘤生长，并提高原位胰腺癌和肺癌模型的生存率，超越传统方法。体内成像显示肿瘤和淋巴结中的上cNP癌细胞@MVDC积聚，促进免疫细胞浸润。机械上,cNPs富集线粒体DNA，增强cGAS-STING介导的DC活化和迁移。我们的策略将冷肿瘤转移到热状态，增强抗肿瘤免疫力，用于潜在的个性化癌症治疗。
