State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Immunol Res. 2015 Feb;3(2):196-205. doi: 10.1158/2326-6066.CIR-14-0177. Epub 2014 Dec 4.
Tumor antigens and innate signals are vital considerations in developing new therapeutic or prophylactic antitumor vaccines. The role or requirement of intact tumor cells in the development of an effective tumor vaccine remains incompletely understood. This study reveals the mechanism by which tumor cell-derived microparticles (T-MP) can act as a cell-free tumor vaccine. Vaccinations with T-MPs give rise to prophylactic effects against the challenge of various tumor cell types, while T-MP-loaded dendritic cells (DC) also exhibit therapeutic effects in various tumor models. Such antitumor effects of T-MPs are perhaps attributable to their ability to generate immune signaling and to represent tumor antigens. Mechanically, T-MPs effectively transfer DNA fragments to DCs, leading to type I IFN production through the cGAS/STING-mediated DNA-sensing pathway. In turn, type I IFN promotes DC maturation and presentation of tumor antigens to T cells for antitumor immunity. These findings highlight a novel tumor cell-free vaccine strategy with potential clinical applications.
肿瘤抗原和先天信号是开发新的治疗性或预防性抗肿瘤疫苗的重要考虑因素。完整的肿瘤细胞在有效肿瘤疫苗开发中的作用或需求仍不完全清楚。本研究揭示了肿瘤细胞衍生的微粒（T-MP）可作为无细胞肿瘤疫苗发挥作用的机制。用 T-MP 进行疫苗接种会产生针对各种肿瘤细胞类型的挑战的预防作用，而负载 T-MP 的树突状细胞（DC）在各种肿瘤模型中也表现出治疗作用。T-MP 的这种抗肿瘤作用可能归因于它们产生免疫信号和代表肿瘤抗原的能力。在机制上，T-MP 可有效地将 DNA 片段转移到 DC 中，通过 cGAS/STING 介导的 DNA 感应途径诱导 I 型 IFN 的产生。反过来，I 型 IFN 促进 DC 的成熟和将肿瘤抗原呈递给 T 细胞以产生抗肿瘤免疫。这些发现强调了一种具有潜在临床应用的新型无肿瘤细胞疫苗策略。
