Rivera-Caraballo Kimberly Ann, Nair Mitra, Lee Tae Jin, Kaur Balveen, Yoo Ji Young
Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Mol Ther Oncolytics. 2022 Jun 6;26:63-75. doi: 10.1016/j.omto.2022.05.013. eCollection 2022 Sep 15.
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.
高级别胶质瘤（HGGs）是致命的中枢神经系统肿瘤，会在脑内迅速扩散，这使得治疗颇具挑战性。整合素是跨膜受体，介导细胞与细胞外基质（ECM）的相互作用、细胞黏附、迁移、生长和存活。它们在HGG恶性肿瘤中的上调及负相关关系使得靶向整合素成为一种可行的治疗选择。整合素在单纯疱疹病毒1（HSV-1）进入细胞的过程中也发挥作用。溶瘤性HSV-1（oHSV）是临床上最先进的溶瘤病毒疗法，相较于包括HGG在内的实体癌的标准癌症治疗，其安全性和疗效更优。随着oHSV获美国食品药品监督管理局（FDA）批准用于治疗黑色素瘤，以及近期在日本获得用于治疗恶性胶质瘤的有条件批准，oHSV在HGG治疗中的应用备受关注。在本综述中，我们系统概述了整合素与oHSV相关的作用，特别关注其针对HGG的治疗潜力。我们讨论了在oHSV治疗过程中靶向整合素的利弊：虽然整合素作为oHSV进入细胞的通道发挥促治疗作用，但它们也介导阻碍oHSV治疗效果的先天性抗病毒免疫反应。我们还进一步讨论了在oHSV治疗背景下调节整合素双重功能的替代策略。
