Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
J Immunol. 2012 Jul 15;189(2):558-66. doi: 10.4049/jimmunol.1200563. Epub 2012 Jun 8.
Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity, and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8(+) T cells. We show in this study that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8(+) T cells, whereas CD4(+) T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8(+) T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that in the absence of irradiation, the activation status of dendritic cells rather than the amount of tumor-derived Ag is the bottleneck, which precludes efficient anti-tumor immunity.
放射疗法是癌症的重要治疗方法。其主要作用模式被认为是对肿瘤细胞 DNA 的不可逆损伤，但有证据表明辐照会动员肿瘤特异性免疫，最近的研究表明，高剂量放射治疗的疗效取决于 CD8(+) T 细胞的存在。在这项研究中，我们表明单次高剂量（10 Gy）放射疗法的疗效取决于树突状细胞和 CD8(+) T 细胞，而 CD4(+) T 细胞或巨噬细胞则可有可无。我们表明，局部高剂量照射会导致肿瘤相关树突状细胞的激活，进而支持肿瘤特异性效应 CD8(+) T 细胞，从而确定了放射治疗诱导肿瘤特异性免疫动员的机制。我们提出，在没有辐照的情况下，树突状细胞的激活状态而不是肿瘤衍生抗原的数量是瓶颈，这阻碍了有效的抗肿瘤免疫。
