Everts Anne, Bergeman Melissa, McFadden Grant, Kemp Vera
Research Program Infection and Immunity, Utrecht University, 3584 CS Utrecht, The Netherlands.
Center for Immunotherapy, Vaccines and Virotherapy (CIVV), The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Biomedicines. 2020 Nov 5;8(11):474. doi: 10.3390/biomedicines8110474.
Current cancer therapeutics often insufficiently eradicate malignant cells due to the surrounding dense tumor stroma. This multi-componential tissue consists of mainly cancer-associated fibroblasts, the (compact) extracellular matrix, tumor vasculature, and tumor-associated macrophages, which all exert crucial roles in maintaining a pro-tumoral niche. Their continuous complex interactions with tumor cells promote tumor progression and metastasis, emphasizing the challenges in tumor therapy development. Over the last decade, advances in oncolytic virotherapy have shown that oncolytic viruses (OVs) are a promising multi-faceted therapeutic platform for simultaneous tumor and stroma targeting. In addition to promoting tumor cell oncolysis and systemic anti-tumor immunity, accumulating data suggest that OVs can also directly target stromal components, facilitating OV replication and spread, as well as promoting anti-tumor activity. This review provides a comprehensive overview of the interactions between native and genetically modified OVs and the different targetable tumor stromal components, and outlines strategies to improve stroma targeting by OVs.
由于周围致密的肿瘤基质，目前的癌症治疗方法往往无法充分根除恶性细胞。这种多成分组织主要由癌症相关成纤维细胞、（致密的）细胞外基质、肿瘤脉管系统和肿瘤相关巨噬细胞组成，它们在维持促肿瘤微环境中都发挥着关键作用。它们与肿瘤细胞持续复杂的相互作用促进肿瘤进展和转移，凸显了肿瘤治疗开发面临的挑战。在过去十年中，溶瘤病毒疗法的进展表明，溶瘤病毒（OVs）是一个有前景的多方面治疗平台，可同时靶向肿瘤和基质。除了促进肿瘤细胞溶解和全身抗肿瘤免疫外，越来越多的数据表明，溶瘤病毒还可以直接靶向基质成分，促进溶瘤病毒的复制和传播，以及增强抗肿瘤活性。本综述全面概述了天然和基因改造的溶瘤病毒与不同可靶向肿瘤基质成分之间的相互作用，并概述了改善溶瘤病毒靶向基质的策略。
