a Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and.
Radiat Res. 2014 Aug;182(2):126-38. doi: 10.1667/RR13374.1. Epub 2014 Jun 24.
There is increasing evidence of the potential for radiation therapy to generate antitumor immune responses. The mechanisms of this immune-activating potential include actions on tumor cells such as immunogenic cell death and phenotypic change. Radiation modulates tumor cell surface expression of cell death receptors, tumor-associated antigens and adhesion molecules. This process of immunomodulation sensitizes tumor cells to immune-mediated killing. Radiation also affects immune compartments, including antigen-presenting cells, cytotoxic T lymphocytes and humoral immunity, leading to specific antitumor immune responses. Recognizing the importance of immunity as a potentiator of response to radiation leads to rational augmentation of antitumor immunity by combining radiation and immunotherapy. Targeted immunotherapy manipulates the immune system in a way that best synergizes with radiation. This article discusses the ability of radiation monotherapy to induce antitumor immunity, with a focus on the effect of radiation on antigen-presenting cells and cytotoxic T lymphocytes. We define two important responses generated by tumor cells, immunogenic cell death and immunomodulation, both of which are radiation dose-dependent. In conclusion, we describe the translation of several combination therapies from the preclinical to the clinical setting and identify opportunities for further exploration.
越来越多的证据表明，放射治疗有可能产生抗肿瘤免疫反应。这种免疫激活潜力的机制包括对肿瘤细胞的作用，如免疫原性细胞死亡和表型改变。放射调节肿瘤细胞表面死亡受体、肿瘤相关抗原和黏附分子的表达。这个免疫调节过程使肿瘤细胞对免疫介导的杀伤敏感。放射还影响免疫细胞群，包括抗原呈递细胞、细胞毒性 T 淋巴细胞和体液免疫，导致特定的抗肿瘤免疫反应。认识到免疫作为增强放疗反应的重要因素，导致通过放疗和免疫治疗的合理联合来增强抗肿瘤免疫。靶向免疫疗法以与放疗最佳协同的方式来调节免疫系统。本文讨论了放射单药治疗诱导抗肿瘤免疫的能力，重点讨论了放射对抗原呈递细胞和细胞毒性 T 淋巴细胞的影响。我们定义了肿瘤细胞产生的两种重要反应，即免疫原性细胞死亡和免疫调节，这两种反应都与辐射剂量有关。总之，我们描述了几种从临床前到临床的联合治疗方法的转化，并确定了进一步探索的机会。
