Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
Cytokine Growth Factor Rev. 2020 Dec;56:69-82. doi: 10.1016/j.cytogfr.2020.07.007. Epub 2020 Sep 1.
In the past two decades there have been substantial advances in understanding the anti-cancer mechanisms of oncolytic viruses (OVs). OVs can mediate their effects directly, by preferentially infecting and killing tumour cells. Additionally, OVs can indirectly generate anti-tumour immune responses. These differing mechanisms have led to a paradoxical divergence in strategies employed to further increase the potency of oncolytic virotherapies. On one hand, the tumour neovasculature is seen as a vital lifeline to the survival of the tumour, leading some to use OVs to target the tumour vasculature in hopes to starve cancers. Therapeutics causing vascular collapse can potentiate tumour hypoxia, nutrient restriction and pro-inflammatory cytokine release, which has shown promise in oncological studies. On the other hand, the same vasculature plays an important role for the dissemination of OVs, trafficking of effector cells and other therapeutics, which has prompted researchers to find ways of normalizing the vasculature to enhance infiltration of leukocytes and delivery of therapeutic agents. This article describes the recent developments of therapies aimed to shut down versus normalize tumour vasculature in order to inform researchers striving to optimize OV-based therapies.
在过去的二十年中，人们对溶瘤病毒（OVs）的抗癌机制有了实质性的认识。OVs 可以通过优先感染和杀死肿瘤细胞来直接发挥作用。此外，OVs 还可以间接产生抗肿瘤免疫反应。这些不同的机制导致了在进一步提高溶瘤病毒疗法效力方面所采用的策略出现了自相矛盾的分歧。一方面，肿瘤新生血管被认为是肿瘤生存的重要生命线，因此一些人使用 OVs 来靶向肿瘤血管，以期饿死癌症。导致血管塌陷的治疗方法会加剧肿瘤缺氧、营养限制和促炎细胞因子的释放，这在肿瘤学研究中显示出了一定的前景。另一方面，同样的血管对于 OVs 的传播、效应细胞和其他治疗药物的运输也起着重要作用，这促使研究人员寻找方法使血管正常化，以增强白细胞的浸润和治疗药物的输送。本文描述了旨在关闭与使肿瘤血管正常化的治疗方法的最新进展，以便为努力优化基于 OV 的治疗方法的研究人员提供信息。
