Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center, Columbus, OH 43210, United States.
Cytokine Growth Factor Rev. 2010 Apr-Jun;21(2-3):127-34. doi: 10.1016/j.cytogfr.2010.02.014.
Interactions between tumor cells and their microenvironment have been shown to play a very significant role in the initiation, progression, and invasiveness of cancer. These tumor-stromal interactions are capable of altering the delivery and effectiveness of therapeutics into the tumor and are also known to influence future resistance and re-growth after treatment. Here we review recent advances in the understanding of the tumor microenvironment and its response to oncolytic viral therapy. The multifaceted environmental response to viral therapy can influence viral infection, replication, and propagation within the tumor. Recent studies have unveiled the complicated temporal changes in the tumor vasculature post-oncolytic virus (OV) treatment, and their impact on tumor biology. Similarly, the secreted extracellular matrix in solid tumors can affect both infection and spread of the therapeutic virus. Together, these complex changes in the tumor microenvironment also modulate the activation of the innate antiviral host immune response, leading to quick and efficient viral clearance. In order to combat these detrimental responses, viruses have been combined with pharmacological adjuvants and "armed" with therapeutic genes in order to suppress the pernicious environmental conditions following therapy. In this review we will discuss the impact of the tumor environment on viral therapy and examine some of the recent literature investigating methods of modulating this environment to enhance oncolysis.
肿瘤细胞与其微环境之间的相互作用已被证明在癌症的发生、进展和侵袭性方面起着非常重要的作用。这些肿瘤-基质相互作用能够改变治疗药物在肿瘤中的传递和效果，并且已知会影响治疗后的未来耐药性和再生长。在这里，我们回顾了对肿瘤微环境及其对溶瘤病毒治疗反应的理解的最新进展。对病毒治疗的多方面环境反应会影响病毒在肿瘤内的感染、复制和传播。最近的研究揭示了溶瘤病毒（OV）治疗后肿瘤血管的复杂时变及其对肿瘤生物学的影响。同样，实体瘤中分泌的细胞外基质也会影响治疗病毒的感染和传播。总之，肿瘤微环境的这些复杂变化也调节了先天抗病毒宿主免疫反应的激活，导致病毒迅速有效地清除。为了对抗这些有害反应，已经将病毒与药理佐剂结合，并“武装”了治疗基因，以抑制治疗后有害的环境条件。在这篇综述中，我们将讨论肿瘤环境对病毒治疗的影响，并研究一些最近的文献，探讨调节这种环境以增强溶瘤的方法。
