Alberta Children's Hospital Research Institute, Calgary, AB, T2N 4N1, Canada.
Arnie Charbonneau Cancer Institute, Calgary, AB, T2N 4N1, Canada.
Commun Biol. 2022 Dec 19;5(1):1385. doi: 10.1038/s42003-022-04254-3.
There is debate in the field of oncolytic virus (OV) therapy, whether a single viral dose, or multiple administrations, is better for tumor control. Using intravital microscopy, we describe the fate of vesicular stomatitis virus (VSV) delivered systemically as a first or a second dose. Following primary administration, VSV binds to the endothelium, initiates tumor infection and activates a proinflammatory response. This initial OV dose induces neutrophil migration into the tumor and limits viral replication. OV administered as a second dose fails to infect the tumor and is captured by intravascular monocytes. Despite a lack of direct infection, this second viral dose, in a monocyte-dependent fashion, enhances and sustains infection by the first viral dose, promotes CD8 T cell recruitment, delays tumor growth and improves survival in multi-dosing OV therapy. Thus, repeated VSV dosing engages monocytes to post-condition the tumor microenvironment for improved infection and anticancer T cell responses. Understanding the complex interactions between the subsequent viral doses is crucial for improving the efficiency of OV therapy and virus-based vaccines.
在溶瘤病毒（OV）治疗领域存在争议，单次病毒剂量或多次给药，哪种方法更有利于肿瘤控制。本研究通过活体显微镜技术，描述了全身性给予水疱性口炎病毒（VSV）作为首剂或第 2 剂的命运。初次给药后，VSV 与内皮细胞结合，引发肿瘤感染并激活炎症反应。首剂 OV 会诱导中性粒细胞迁移到肿瘤中，并限制病毒复制。第 2 剂 OV 给药无法感染肿瘤，而是被血管内的单核细胞捕获。尽管没有直接感染，但第 2 剂病毒以单核细胞依赖的方式增强和维持了第 1 剂病毒的感染，促进 CD8 T 细胞募集，延迟肿瘤生长并提高多次 OV 治疗的存活率。因此，重复给予 VSV 会激活单核细胞，对肿瘤微环境进行后处理，以改善感染和抗肿瘤 T 细胞反应。了解后续病毒剂量之间的复杂相互作用对于提高 OV 治疗和基于病毒的疫苗的效率至关重要。
