The number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons. However, high-linear energy transfer (LET) particles, mainly carbon ions, are of special interest for application in radiotherapy, as their special physical features result in high precision and hence lower toxicity, and at the same time in increased efficiency in cell inactivation in the target region, i.e., the tumor. The radiobiology of high-LET particles differs with respect to DNA damage repair, cytogenetic damage, and cell death type, and their increased LET can tackle cells’ resistance to hypoxia. Recent developments and perspectives, e.g., the return of high-LET particle therapy to the US with a center planned at Mayo clinics, the application of carbon ion radiotherapy using cost-reducing cyclotrons and the application of helium is foreseen to increase the interest in this type of radiotherapy. However, further preclinical research is needed to better understand the differential radiobiological mechanisms as opposed to photon radiotherapy, which will help to guide future clinical studies for optimal exploitation of high-LET particle therapy, in particular related to new concepts and innovative approaches. Herein, we summarize the basics and recent progress in high-LET particle radiobiology with a focus on carbon ions and discuss the implications of current knowledge for charged-particle radiotherapy. We emphasize the potential of high-LET particles with respect to immunogenicity and especially their combination with immunotherapy.

全球接受带电粒子放射治疗的患者数量以及治疗中心的数量正在增加，尤其是质子治疗。然而，高线性能量转移（LET）颗粒（主要是碳离子）在放射治疗中的应用特别令人感兴趣，因为它们特殊的物理特性导致高精度，从而降低毒性，同时提高细胞灭活效率在目标区域，即肿瘤。高 LET 颗粒的放射生物学在 DNA 损伤修复、细胞遗传学损伤和细胞死亡类型方面有所不同，它们增加的 LET 可以解决细胞对缺氧的抵抗力。最近的发展和前景，例如，高 LET 粒子治疗返回美国并计划在梅奥诊所设立一个中心，使用降低成本的回旋加速器进行碳离子放射治疗的应用以及氦气的应用预计将增加对此的兴趣放射治疗的类型。然而，需要进一步的临床前研究来更好地了解与光子放射治疗不同的放射生物学机制，这将有助于指导未来的临床研究，以优化利用高 LET 粒子治疗，特别是与新概念和创新方法相关的研究。在此，我们总结了高 LET 粒子放射生物学的基础知识和最新进展，重点关注碳离子，并讨论了当前知识对带电粒子放射治疗的影响。我们强调高 LET 颗粒在免疫原性方面的潜力，特别是它们与免疫疗法的结合。