Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Sackler Faculty of Exact Sciences, School of Physics and Astronomy, Tel Aviv University, Tel Aviv 6997801, Israel.
Cells. 2021 Jan 25;10(2):228. doi: 10.3390/cells10020228.
The delivery of radiation therapy (RT) for cancer with intent to cure has been optimized and standardized over the last 80 years. Both preclinical and clinical work emphasized the observation that radiation destroys the tumor and exposes its components to the immune response in a mode that facilitates the induction of anti-tumor immunity or reinforces such a response. External beam photon radiation is the most prevalent in situ abolition treatment, and its use exposed the "abscopal effect". Particle radiotherapy (PRT), which has been in various stages of research and development for 70 years, is today available for the treatment of patients in the form of alpha particles, proton, or carbon ion radiotherapy. Charged particle radiotherapy is based on the acceleration of charged species, such as protons or carbon-12, which deposit their energy in the treated tumor and have a higher relative biological effectiveness compared with photon radiation. In this review, we will bring evidence that alpha particles, proton, or carbon ion radiation can destroy tumors and activate specific anti-tumor immune responses. Radiation may also directly affect the distribution and function of immune cells such as T cells, regulatory T cells, and mononuclear phagocytes. Tumor abolition by radiation can trigger an immune response against the tumor. However, abolition alone rarely induces effective anti-tumor immunity resulting in systemic tumor rejection. Immunotherapy can complement abolition to reinforce the anti-tumor immunity to better eradicate residual local and metastatic tumor cells. Various methods and agents such as immunoadjuvants, suppressor cell inhibitors, or checkpoint inhibitors were used to manipulate the immune response in combination with radiation. This review deals with the manifestations of particle-mediated radiotherapy and its correlation with immunotherapy of cancer.
在过去的 80 年中，癌症的放射治疗（RT）的目的是治愈，其已经得到了优化和标准化。临床前和临床工作都强调了这样一种观察结果，即放射破坏肿瘤，并以促进抗肿瘤免疫或增强这种反应的方式将其成分暴露于免疫反应中。外照射光子辐射是最常见的原位消除治疗方法，其应用暴露了“远隔效应”。粒子放射治疗（PRT）已经处于研究和开发的各个阶段 70 年，今天可用于以α粒子、质子或碳离子放射治疗的形式治疗患者。带电粒子放射治疗基于带电粒子（如质子或碳-12）的加速，这些带电粒子将其能量沉积在治疗的肿瘤中，与光子辐射相比具有更高的相对生物学效应。在这篇综述中，我们将提供证据表明，α粒子、质子或碳离子辐射可以破坏肿瘤并激活特定的抗肿瘤免疫反应。辐射还可能直接影响免疫细胞（如 T 细胞、调节性 T 细胞和单核吞噬细胞）的分布和功能。放射治疗引起的肿瘤消除可以引发针对肿瘤的免疫反应。然而，仅消除很少能诱导有效的抗肿瘤免疫，导致全身肿瘤排斥。免疫疗法可以与消除疗法互补，以增强抗肿瘤免疫，从而更好地消灭残留的局部和转移性肿瘤细胞。各种方法和试剂，如免疫佐剂、抑制细胞抑制剂或检查点抑制剂，已被用于与放射治疗联合操纵免疫反应。这篇综述涉及粒子介导的放射治疗的表现及其与癌症免疫治疗的相关性。
