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.

实体癌能够逃脱免疫监视，并且对免疫疗法中的当前治疗有抵抗力。最近的证据表明干扰素基因（STING）途径的刺激剂在抗肿瘤免疫中的关键作用。STING靶向激活已被广泛研究作为一种新的癌症治疗策略。以前，我们报道了一种安全有效的STING激活纳米疫苗，可在多种肿瘤模型中增强全身性肿瘤特异性T细胞应答。据报道，局部放疗不仅可以减轻肿瘤负担，还可以以STING依赖的方式增强局部抗肿瘤免疫力。在这项研究中，我们证明这两种方式的组合会导致协同反应，并在两种小鼠肿瘤模型中长期消退大型已确立的肿瘤。CD8 ⁺的百分比联合治疗后，原发性肿瘤中的T细胞显着增加。从机理上讲，放疗和纳米疫苗的增强T细胞反应是STING途径依赖性的。此外，纳米疫苗与放射疗法协同作用，可在远端肿瘤中实现更好的治疗效果。这些发现表明，局部放疗与全身性PC7A纳米疫苗的结合为改善晚期实体癌的治疗效果提供了有用的策略。