The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.
The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.
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DOI：
10.1016/j.omto.2022.05.013
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发表时间：
2022-09-15
期刊：
影响因子：
--
通讯作者：
Yoo, Ji Young
中科院分区：
文献类型：
--
作者：
Rivera-Caraballo, Kimberly Ann;Nair, Mitra;Lee, Tae Jin;Kaur, Balveen;Yoo, Ji Young
高级别胶质瘤(HGG)是一种致命的中枢神经系统肿瘤，它可以迅速扩散到整个大脑，使治疗具有挑战性。整合素是介导细胞-细胞外基质(ECM)相互作用、细胞黏附、迁移、生长和存活的跨膜受体。它们在HGG恶性肿瘤中的上调和负相关性使靶向整合素成为一种可行的治疗选择。整合素也在单纯疱疹病毒1型(HSV-1)进入过程中发挥作用。溶瘤单纯疱疹病毒1型(OHSV)是临床上最先进的溶瘤病毒疗法，与标准的实体癌治疗(包括HGG)相比，显示出更好的安全性和有效性。随着FDA批准OHSV治疗黑色素瘤，以及最近日本有条件地批准OHSV治疗恶性胶质瘤，使用OHSV治疗HGG已引起人们的极大兴趣。在这篇综述中，我们系统地概述了整合素在OHSV中的作用，特别是它对HGG的治疗潜力。我们讨论了在OHSV治疗中靶向整合素的利弊：虽然整合素作为OHSV进入的门户发挥了促进治疗的作用，但它们也介导了阻碍OHSV治疗效果的先天抗病毒免疫反应。我们进一步讨论在OHSV治疗的背景下调节整合素的双重功能的替代策略。整合素介导细胞外到细胞内的信号转导，对HSV-1的进入非常重要。虽然后者对于有效的OHSV治疗结果至关重要，但它可能导致不良的抗病毒免疫反应。因此，在保持病毒进入效率的同时，微调整合素对OHSV的拮抗作用，将促进抗肿瘤反应，从而最大限度地发挥OHSV的治疗效果。
High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of oHSV for malignant glioma in Japan, usage of oHSV for HGG has become of great interest. In this review, we provide a systematic overview of the role of integrins in relation to oHSV, with a special focus on its therapeutic potential against HGG. We discuss the pros and cons of targeting integrins during oHSV therapy: while integrins play a pro-therapeutic role by acting as a gateway for oHSV entry, they also mediate the innate antiviral immune responses that hinder oHSV therapeutic efficacy. We further discuss alternative strategies to regulate the dual functionality of integrins in the context of oHSV therapy. Integrins mediate extracellular-to-intracellular signaling and are important for HSV-1 entry. Although the latter is crucial for an efficacious oHSV therapeutic outcome, it can lead to undesirable antiviral immune responses. Therefore, fine-tuning the antagonistic effects of integrins against oHSV while maintaining viral entry efficiency will promote the antitumoral response to maximize oHSV therapeutic efficacy.
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