Radiation Oncology Unit, First Department of Radiology, Medical School, Aretaieion Hospital, National and Kapodistrian University of Athens (NKUOA), Athens, Greece.
Department of Pathology, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Int J Radiat Biol. 2023;99(5):715-736. doi: 10.1080/09553002.2023.2144960. Epub 2022 Nov 16.
Radiotherapy (RT) and immunotherapy are powerful anti-tumor treatment modalities. Experimental research has demonstrated an important interplay between the cytotoxic effects of RT and the immune system. This systematic review provides an overview of the basics of anti-tumor immunity and focuses on the mechanisms underlying the interplay between RT and immune anti-tumor response that set the molecular basis of immuno-RT.
An 'immunity acquired equilibrium' mimicking tumor dormancy can be achieved post-irradiation treatment, with the balance shifted toward tumor eradication or regrowth when immune cells' cytotoxic effects or cancer proliferation rate prevail, respectively. RT has both immunosuppressive and immune-enhancing properties. The latter effect is also known as radio-vaccination. Its mechanisms involve up- or down-regulation of membrane molecules, such as PD-L1, HLA-class-I, CD80/86, CD47, and Fas/CD95, that play a vital role in immune checkpoint pathways and increased cytokine expression (e.g. INFα,β,γ, IL1,2, and TNFα) by cancer or immune cells. Moreover, the interactions of radiation with the tumor microenvironment (fibroblasts, tumor-infiltrating lymphocytes, monocytes, and dendritic cells are also an important component of radio-vaccination. Thus, RT may have anti-tumor vaccine properties, whose sequels can be exploited by immunotherapy agents to treat different cancer subtypes effectively.
放射治疗（RT）和免疫疗法是强大的抗肿瘤治疗方法。实验研究表明，RT 的细胞毒性作用和免疫系统之间存在重要的相互作用。本系统评价概述了抗肿瘤免疫的基础知识，并重点介绍了 RT 与免疫抗肿瘤反应相互作用的机制，这些机制为免疫 RT 的分子基础奠定了基础。
放射治疗后可达到类似于肿瘤休眠的“获得性免疫平衡”，当免疫细胞的细胞毒性作用或癌症增殖率占优势时，平衡分别向肿瘤消除或生长方向转移。RT 具有免疫抑制和免疫增强特性。后者也称为放射疫苗接种。其机制包括膜分子（如 PD-L1、HLA 类-I、CD80/86、CD47 和 Fas/CD95）的上调或下调，这些分子在免疫检查点途径和细胞因子表达（例如 INFα、β、γ、IL1、2 和 TNFα）中发挥重要作用由癌症或免疫细胞。此外，辐射与肿瘤微环境（成纤维细胞、肿瘤浸润淋巴细胞、单核细胞和树突状细胞）的相互作用也是放射疫苗接种的重要组成部分。因此，RT 可能具有抗肿瘤疫苗特性，其后续作用可以被免疫治疗剂利用，以有效地治疗不同的癌症亚型。
