Oncology & Radiotherapy Department, Zhejiang Hospital, Hangzhou, China.
Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Cancer Med. 2023 Feb;12(3):3201-3221. doi: 10.1002/cam4.5085. Epub 2022 Jul 31.
Within the field of oncotherapy, research interest regarding immunotherapy has risen to the point that it is now seen as a key application. However, inherent disadvantages of immune checkpoint inhibitors (ICIs), such as their low response rates and immune-related adverse events (irAEs), currently restrict their clinical application. Were these disadvantages to be overcome, more patients could derive prolonged benefits from ICIs. At present, many basic experiments and clinical studies using hyperthermia combined with ICI treatment (HIT) have been performed and shown the potential to address the above challenges. Therefore, this review extensively summarizes the knowledge and progress of HIT for analysis and discusses the effect and feasibility.
In this review, we explored the PubMed and clinicaltrials.gov databases, with regard to the searching terms "immune checkpoint inhibitor, immunotherapy, hyperthermia, ablation, photothermal therapy".
By reviewing the literature, we analyzed how hyperthermia influences tumor immunology and improves the efficacy of ICI. Hyperthermia can trigger a series of multifactorial molecular cascade reactions between tumors and immunization and can significantly induce cytological modifications within the tumor microenvironment (TME). The pharmacological potency of ICIs can be enhanced greatly through the immunomodulatory amelioration of immunosuppression, and the activation of immunostimulation. Emerging clinical trials outcome regarding HIT have verified and enriched the theoretical foundation of synergistic sensitization.
HIT research is now starting to transition from preclinical studies to clinical investigations. Several HIT sensitization mechanisms have been reflected and demonstrated as significant survival benefits for patients through pioneering clinical trials. Further studies into the theoretical basis and practical standards of HIT, combined with larger-scale clinical studies involving more cancer types, will be necessary for the future.
在肿瘤治疗领域，免疫疗法的研究兴趣已经上升到一个关键应用的程度。然而，免疫检查点抑制剂（ICIs）存在固有缺点，如低反应率和免疫相关不良事件（irAEs），目前限制了其临床应用。如果克服了这些缺点，更多的患者将从 ICI 中获得更长时间的益处。目前，已经进行了许多使用热疗联合 ICI 治疗（HIT）的基础实验和临床研究，显示出解决上述挑战的潜力。因此，本综述广泛总结了 HIT 的知识和进展，进行了分析，并讨论了其效果和可行性。
在本综述中，我们探索了 PubMed 和 clinicaltrials.gov 数据库，使用的搜索词为“immune checkpoint inhibitor, immunotherapy, hyperthermia, ablation, photothermal therapy”。
通过对文献的回顾，我们分析了热疗如何影响肿瘤免疫学并提高 ICI 的疗效。热疗可以在肿瘤和免疫之间引发一系列多因素分子级联反应，并能显著诱导肿瘤微环境（TME）中的细胞学改变。通过免疫抑制的免疫调节改善和免疫刺激的激活，ICIs 的药理学效力可以大大增强。关于 HIT 的新兴临床试验结果验证并丰富了协同增敏的理论基础。
HIT 的研究现在开始从基础研究转向临床研究。通过开创性的临床试验，已经反映并证明了几种 HIT 增敏机制为患者带来了显著的生存获益。未来需要进一步研究 HIT 的理论基础和实践标准，并结合更多癌症类型的更大规模的临床研究。
