肿瘤细胞治疗研究
英文原题：Leveraging multimodal cancer immunotherapy to amplify the efficacy of oncolytic viruses.
这些方法展示了多模式免疫疗法如何克服OVs的内在局限性，从而实现持久的抗肿瘤免疫。
溶瘤病毒（OVs）代表了一种多功能的癌症免疫治疗平台，能够选择性感染并裂解肿瘤细胞，同时触发全身性抗肿瘤免疫。然而，其治疗效果仍受到抗病毒免疫、瘤内扩散受限以及免疫抑制性肿瘤微环境的限制。本综述重点介绍了通过与互补性免疫疗法合理联合来增强OV疗效的新兴策略，包括免疫检查点抑制剂、过继性细胞疗法、癌症疫苗和小分子免疫调节剂。这些协同干预措施可以重塑肿瘤微环境、增强免疫细胞浸润和活化、逆转免疫抑制性反馈、促进免疫原性细胞死亡、使肿瘤血管正常化以及调节肠道微生物群，从而共同放大OV的复制和溶瘤效力。人工智能和多组学分析的整合进一步实现了精准的患者分层和联合方案的优化。与此同时，先进的工程化策略，如为OVs装备免疫调节转基因和减轻宿主抗病毒反应，进一步强化了这些效果。总之，这些方法展示了多模式免疫治疗如何克服OVs的固有局限性，从而实现持久的抗肿瘤免疫。本综述强调了联合策略在基于OV的免疫肿瘤学中的核心作用，并展望了加速其临床转化的未来方向。
Oncolytic viruses (OVs) represent a versatile platform for cancer immunotherapy, capable of selectively infecting and lysing tumor cells while triggering systemic antitumor immunity. However, their therapeutic efficacy remains limited by antiviral immunity, restricted intratumoral spread, and an immunosuppressive tumor microenvironment. This review highlights emerging strategies to potentiate OV efficacy through rational combination with complementary immunotherapies, including immune checkpoint inhibitors, adoptive cell therapies, cancer vaccines, and small-molecule immunomodulators. These synergistic interventions can remodel the tumor microenvironment, enhance immune cell infiltration and activation, reverse immunosuppressive feedback, promote immunogenic cell death, normalize the tumor vasculature, and modulate the gut microbiota, collectively amplifying OV replication and oncolytic potency. The integration of artificial intelligence and multiomics profiling further enables precise patient stratification and optimization of combination regimens. In parallel, advanced engineering strategies, such as arming OVs with immunomodulatory transgenes and mitigating host antiviral responses, further reinforce these effects. Together, these approaches illustrate how multimodal immunotherapy can overcome the intrinsic limitations of OVs, enabling durable antitumor immunity. This review underscores the central role of combination strategies in OV-based immuno-oncology and outlines future directions to accelerate their clinical translation.
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