Das Krishna, Urbiola Carles, Spiesschaert Bart, Mueller Philipp, Wollmann Guido
Division of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Innsbruck, Austria.
Methods Mol Biol. 2020;2058:155-177. doi: 10.1007/978-1-4939-9794-7_10.
In addition of being directly tumoricidal, oncolytic viruses have emerged as potent partners for established and investigational immunotherapies due to their immune-stimulatory effects. The shifting focus on virus-mediated immune modulation calls for a comprehensive analysis of the tumor microenvironment (TME) and the factors orchestrating the antiviral and antitumor immune response. The oncolytic VSV-GP studied in our lab is a safe and potent antitumor agent with a fast replication cycle and killing of a broad range of different cancer types. It induces a robust local inflammatory conversion of the TME and drives a strong adaptive immune response toward the tumor. Here we present our multidisciplinary approach to study VSV-GP treatment effects in tumors by assessing both immune cells (tumor-infiltrating lymphocytes and tumor-associated macrophages) and immune-regulatory factors (cytokines) as well as characterizing immune signatures using an immune-targeted NanoString gene expression system.
除了具有直接杀瘤作用外,溶瘤病毒因其免疫刺激作用,已成为既定和研究中的免疫疗法的有力伙伴。对病毒介导的免疫调节的关注转变,需要对肿瘤微环境(TME)以及协调抗病毒和抗肿瘤免疫反应的因素进行全面分析。我们实验室研究的溶瘤水疱性口炎病毒糖蛋白(VSV-GP)是一种安全有效的抗肿瘤药物,具有快速复制周期,能杀死多种不同类型的癌症。它能诱导TME发生强烈的局部炎症转变,并驱动针对肿瘤的强大适应性免疫反应。在此,我们展示了我们的多学科方法,通过评估免疫细胞(肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞)和免疫调节因子(细胞因子)以及使用免疫靶向的NanoString基因表达系统来表征免疫特征,从而研究VSV-GP在肿瘤中的治疗效果。