He Mengying, Wang Mengyuan, Xu Tao, Zhang Mengyao, Dai Huaxing, Wang Chao, Ding Dawei, Zhong Zhiyuan
Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin D02 NY74, Ireland.
J Control Release. 2023 Apr;356:623-648. doi: 10.1016/j.jconrel.2023.02.040. Epub 2023 Mar 21.
Reactive oxygen species (ROS) are crucial signaling molecules that can arouse immune system. In recent decades, ROS has emerged as a unique therapeutic strategy for malignant tumors as (i) it can not only directly reduce tumor burden but also trigger immune responses by inducing immunogenic cell death (ICD); and (ii) it can be facilely generated and modulated by radiotherapy, photodynamic therapy, sonodynamic therapy and chemodynamic therapy. The anti-tumor immune responses are, however, mostly downplayed by the immunosuppressive signals and dysfunction of effector immune cells within the tumor microenvironment (TME). The past years have seen fierce developments of various strategies to power ROS-based cancer immunotherapy by e.g. combining with immune checkpoints inhibitors, tumor vaccines, and/or immunoadjuvants, which have shown to potently inhibit primary tumors, metastatic tumors, and tumor relapse with limited immune-related adverse events (irAEs). In this review, we introduce the concept of ROS-powered cancer immunotherapy, highlight the innovative strategies to boost ROS-based cancer immunotherapy, and discuss the challenges in terms of clinical translation and future perspectives.
活性氧（ROS）是能够激发免疫系统的关键信号分子。近几十年来，ROS已成为一种独特的恶性肿瘤治疗策略，原因如下：（i）它不仅可以直接减轻肿瘤负担，还能通过诱导免疫原性细胞死亡（ICD）引发免疫反应；（ii）放疗、光动力疗法、声动力疗法和化学动力疗法能够轻松地产生并调节ROS。然而，肿瘤微环境（TME）中的免疫抑制信号和效应免疫细胞功能障碍大多会削弱抗肿瘤免疫反应。在过去几年中，人们大力发展了各种策略来增强基于ROS的癌症免疫疗法，例如与免疫检查点抑制剂、肿瘤疫苗和/或免疫佐剂联合使用，这些策略已显示出能有效抑制原发性肿瘤、转移性肿瘤和肿瘤复发，且免疫相关不良事件（irAE）有限。在本综述中，我们介绍了ROS驱动的癌症免疫疗法的概念，强调了增强基于ROS的癌症免疫疗法的创新策略，并讨论了临床转化方面的挑战和未来前景。
