Cheng Chong, Wang Qingzhe, Zhang Shuang
Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2025 Jul 8;16:1610858. doi: 10.3389/fimmu.2025.1610858. eCollection 2025.
Oncolytic viruses (OVs) offer a promising antitumor strategy by selectively lysing tumor cells and simultaneously activating innate and adaptive immune responses. Recent studies have shed light on the immunostimulatory mechanisms of OVs, particularly oncolytic adenovirus (OAds), which are emerging as leading candidates due to their favorable safety profile, genomic stability, and efficient transduction capacity. Despite the significant progress made by immune checkpoint inhibitors (ICIs) in antitumor therapy, treatment resistance continues to be a major barrier to their clinical effectiveness. OVs and ICIs work synergistically: OVs reprogram the immunosuppressive tumor microenvironment (TME) through immune cell recruitment and pro-inflammatory cytokine production, potentially overcoming ICI resistance. In turn, ICIs enhance T cell function by blocking inhibitory signaling pathways. This review highlights recent preclinical and clinical advancements in the therapeutic potential of combining OAds with ICIs, while also addressing critical translational challenges. We propose a strategic framework for optimizing the development and clinical trial design of these combination therapies to advance precision immunotherapy.
溶瘤病毒（OVs）通过选择性裂解肿瘤细胞并同时激活先天性和适应性免疫反应，提供了一种很有前景的抗肿瘤策略。最近的研究揭示了OVs的免疫刺激机制，特别是溶瘤腺病毒（OAds），由于其良好的安全性、基因组稳定性和高效的转导能力，正成为主要的候选病毒。尽管免疫检查点抑制剂（ICIs）在抗肿瘤治疗方面取得了重大进展，但治疗耐药性仍然是其临床疗效的主要障碍。OVs和ICIs协同作用：OVs通过免疫细胞募集和促炎细胞因子产生来重新编程免疫抑制性肿瘤微环境（TME），有可能克服ICI耐药性。反过来，ICIs通过阻断抑制性信号通路增强T细胞功能。本综述重点介绍了将OAds与ICIs联合应用的治疗潜力的近期临床前和临床进展，同时也探讨了关键的转化挑战。我们提出了一个战略框架，以优化这些联合疗法的开发和临床试验设计，推进精准免疫治疗。
