神经胶质瘤是人脑中最常见的原发性肿瘤，占中枢神经系统恶性肿瘤的81%，当前标准疗法仍是手术切除及术后放化疗。因神经胶质瘤具有高侵袭性、分子异质性、治疗后耐药肿瘤干细胞可再生，以及化疗药物难以通过血脑屏障（BBB）达到足够高的治疗浓度等特点，导致其预后非常差，患者中位存活期仅为15个月。近年来，新兴的溶瘤病毒免疫疗法治疗神经胶质瘤的研究备受关注并取得一定进展，但依然面临诸如BBB、免疫“冷”微环境、宿主抗病毒反应和肿瘤高度异质性等挑战。这些问题限制了溶瘤病毒疗法的深入发展及进一步应用，但也给基础与临床研究者带来新的研究机遇。因此，本文从穿越BBB、改善肿瘤微环境（TME）、调控溶瘤病毒介导的宿主免疫反应和适应肿瘤异质性等四个方面，阐述溶瘤病毒在抗神经胶质瘤治疗研究中的存在问题及对策。

Glioma are the most common primary tumors in the brain, accounting for 81% of central nervous system malignancies. The current standard of care for patients with glioma is still surgical resection and postoperative radiochemotherapy. However, the prognosis of glioma is very poor with a median survival of only 15 months due to its highly aggressive nature, molecular heterogeneity,reproducibility of resistant cancer stem after therapy, and difficulty in crossing the blood-brain barrier (BBB) for chemotherapeutic agents to reach sufficiently high therapeutic levels. In recent years, the emerging oncolytic viruses (OVs) immunotherapy in the treatment of glioma has received much attention and made some progress. Nevertheless, multiple challenges still exist, such as crossing BBB, immune "cold" microenvironment, host antiviral response, and high tumor heterogeneity. These problems limit the further development and applications of oncolytic virus therapy but also bring new research opportunities to basic and clinical researchers.Therefore, this review summarizes the problems and countermeasures in the research and application of oncolytic virus in anti-glioma therapy from four aspects including crossing the BBB, improving the tumor microenvironment, adjusting the host immune responses mediated by oncolytic viruses, and adapting to tumor heterogeneity.

深圳市科创委基础研究项目（No. JCYJ20210324094611031，No. JCYJ20180507182253653）；广东省基础与应用基础研究基金委员会-粤深联合青年基金项目（No. 2022A1515111143)