Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy
Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy
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PC7A 纳米疫苗和电离辐射协同激活 STING 可改善癌症免疫治疗。
DOI：
10.1016/j.jconrel.2019.02.036
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发表时间：
2019-04-28
影响因子：
10.8
通讯作者：
Gao, Jinming
中科院分区：
文献类型：
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作者：
Luo, Min;Liu, Zhida;Gao, Jinming
实体癌能够逃脱免疫监视，并对目前的免疫疗法产生抵抗力。近年来的研究表明，干扰素基因刺激物(STING)通路在抗肿瘤免疫中起着重要作用。刺激靶向激活作为一种新的癌症治疗策略被广泛研究。此前，我们报道了一种安全有效的刺激性纳米疫苗，可以在多种肿瘤模型中增强全身肿瘤特异性T细胞反应。据报道，局部放射治疗不仅减轻了肿瘤负担，而且以一种刺痛依赖的方式增强了局部抗肿瘤免疫。在这项研究中，我们在两个小鼠肿瘤模型中证明了这两种方式的结合导致了大的已建立的肿瘤的长期消退的协同反应。联合治疗后，CD8(+)T细胞在原发肿瘤中的百分率明显升高。从机制上讲，放射治疗和纳米疫苗增强的T细胞反应是STING途径依赖的。此外，纳米疫苗与放射治疗有协同作用，对远端肿瘤有更好的治疗效果。这些发现表明，局部放疗和全身PC7A纳米疫苗的结合为改善晚期实体癌的治疗结果提供了一种有用的策略。
Solid cancers are able to escape immune surveillance and are resistant to current treatment in immunotherapy. Recent evidence indicates the critical role of the stimulator of interferon genes (STING) pathway in antitumor immunity. STING-targeted activation is extensively investigated as a new strategy for cancer therapy. Previously, we reported a safe and efficacious STING-activating nanovaccine to boost systemic tumor-specific T cell responses in multiple tumor models. Local radiotherapy has been reported to not only reduce tumor burden but also enhance local antitumor immunity in a STING-dependent manner. In this study, we demonstrate that combination of these two modalities leads to a synergistic response with long-term regression of large established tumors in two mouse tumor models. The percentage of CD8(+) T cells increased significantly in primary tumors after combination therapy. Mechanistically, the augmented T cell responses of radiotherapy and nanovaccine is STING pathway dependent. Furthermore, nanovaccine synergizes with radiotherapy to achieve a better therapeutic effect in distal tumors. These findings suggest that combination of local radiotherapy with systemic PC7A nanovaccine offers a useful strategy to improve the therapeutic outcome of late stage solid cancers.