溶瘤病毒助力肿瘤免疫治疗  

Oncolytic viruses facilitate tumor immunotherapy

作　　者：杨钰婕 王忆安 吴洁[1,3] 龚朝建[4] 曾朝阳[1,2] 郭文佳[3] 熊炜 YANG YuJie;WANG YiAn;WU Jie;GONG ZhaoJian;ZENG ZhaoYang;GUO WenJia;XIONG Wei(NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education,Cancer Research Institute,Central South University,Changsha 410083,China;The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province,School of Medicine,Hunan Normal University,Changsha 410013,China;Xinjiang Key Laboratory of Translational Biomedical Engineering,Departments of Cancer Research Institute,Affiliated Cancer Hospital of Xinjiang Medical University,Urumqi 830000,China;Department of Oral and Maxillofacial Surgery,the Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学肿瘤研究所,国家卫生健康委员会癌变原理重点实验室,癌变与侵袭原理教育部重点实验室,长沙410083 [2]湖南师范大学医学院,模式动物与干细胞生物学湖南省重点实验室,长沙410013 [3]新疆医科大学附属肿瘤医院,新疆维吾尔自治区肿瘤防治研究所,新疆医工创新研究与生物医药转化重点实验室,乌鲁木齐830000 [4]中南大学湘雅二医院口腔颌面外科,长沙410011

出　　处：《中国科学：生命科学》2024年第11期2037-2050,共14页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:82372811,82303126);湖南省自然科学基金(批准号:2022JJ30063,2024JJ6325)资助。

摘　　要：肿瘤的治疗手段包括手术治疗、放化疗、靶向治疗和免疫治疗等.其中,免疫治疗因为其应用范围广、效果好、副作用低等优势,在肿瘤治疗领域广受关注.但是一些肿瘤中存在免疫激活机制缺陷,即我们常说的“冷肿瘤”,限制了免疫治疗的效果.溶瘤病毒是经基因改造后的一类发挥抗肿瘤作用的病毒,因其具有优秀的免疫激活功能而广受关注,可以使“冷”肿瘤转化为“热”肿瘤.目前研究发现溶瘤病毒可以通过直接杀伤肿瘤细胞提升组织的免疫原性,上调肿瘤细胞表面免疫检查点的表达,以及通过溶瘤病毒的病毒特性激活免疫反应.此外,它们还可在基因工程技术的加持下进一步募集肿瘤浸润T细胞、促进树突状细胞成熟、诱导多能T细胞.因此,我们认为溶瘤病毒将是未来肿瘤免疫治疗的优秀协助者,能很好地放大免疫治疗的抗肿瘤效果.在这篇综述中,我们总结了目前溶瘤病毒的免疫激活机制,并结合临床试验结果展示了溶瘤病毒在免疫治疗中强大的抗肿瘤效果.Tumor immunotherapy,distinguished by its broad applicability,positive outcomes,and minimal side effects,has garnered significant attention recently.However,some tumors exhibit immune escape mechanisms,referred to as“cold”tumors,which curtail the efficacy of immunotherapy.Oncolytic viruses,genetically modified viruses with potent anti-tumor effects,have emerged surprisingly and prominently due to their remarkable immune-activating properties,capable of transforming“cold”tumors into“hot”ones.Current research underscores that oncolytic viruses can enhance tissue immunogenicity by directly eliminating tumor cells,upregulating immune checkpoints on the tumor cell surface,and activating immunity through innate viral properties.Furthermore,through genetic engineering technology,these viruses prompt tumor-infiltrating lymphocyte recruitment,facilitate dendritic cells maturation,and induce T cell activation.The consensus is that oncolytic viruses hold immense potential as facilitators of tumor immunotherapy,amplifying the anti-tumor effects of immunotherapies.This review provides an overview of the current immune activation mechanisms of oncolytic viruses,highlighting their robust anti-tumor effects in clinical applications.

关 键 词：溶瘤病毒 免疫逃逸 免疫治疗 免疫检查点抑制剂 

分 类 号：R730.51[医药卫生—肿瘤]