Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated
Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated
复制标题
DOI：
10.1016/j.ijrobp.2003.09.012
复制
发表时间：
2004-03-01
影响因子：
7
通讯作者：
Formenti, SC
中科院分区：
文献类型：
--
作者：
Demaria, S;Ng, B;Formenti, SC
目的：电离辐射可以减少辐射场外的肿瘤生长，称为远隔效应。尽管在多种恶性肿瘤中已有报道，但远隔效应仍然是一种罕见且知之甚少的事件。电离辐射会产生炎症信号，原则上可以提供来自垂死细胞的肿瘤特异性抗原和树突状细胞激活肿瘤特异性 T 细胞所必需的成熟刺激。因此，我们测试了辐射引起的远隔效应是免疫介导的假设。这是通过使用生长因子 Flt3-配体 (Flt3-L) 增加可用树突状细胞的数量来直接测试的。方法和材料：在两个 Hanks 中携带同基因乳腺癌 67NR 的小鼠，在以 2 或 6 Gy 单剂量对 2 个肿瘤中的 1 个进行局部放射治疗 (RT) 后，每天使用 Flt3-L 治疗 10 天。第二个未照射的肿瘤用作远隔效应的指标。使用重复测量回归分析数据。结果：正如预期的那样，单独放疗仅导致受照射的 67NR 肿瘤生长延迟。令人惊讶的是，RT 和 Flt3-L 的组合也损害了未照射肿瘤的生长。作为对照，Flt3-L 在没有 RT 的情况下没有效果。重要的是，远隔效应被证明是肿瘤特异性的，因为在含有经过治疗的 67NR 肿瘤的同一小鼠中，未照射的 A20 淋巴瘤的生长没有受到影响。此外，当用 RT 加 Flt3-L 治疗 T 细胞缺陷（裸）小鼠时，未观察到未辐射 67NR 肿瘤的生长延迟。 结论：这些结果表明远隔效应部分是免疫介导的，并且需要 T 细胞来介导辐射诱导的远处肿瘤抑制。 (C) 2004 年爱思唯尔公司。
Purpose: Ionizing radiation can reduce tumor growth outside the field of radiation, known as the abscopal effect. Although it has been reported in multiple malignancies, the abscopal effect remains a rare and poorly understood event. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. We therefore tested the hypothesis that the abscopal effect elicited by radiation is immune mediated. This was directly tested by enhancing the number of available dendritic cells using the growth factor Flt3-Ligand (Flt3-L).Methods and Materials: Mice bearing a syngeneic mammary carcinoma, 67NR, in both Hanks were treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only I of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor was used as indicator of the abscopal effect. Data were analyzed using repeated measures regression.Results: RT alone led to growth delay exclusively of the irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L had no effect without RT. Importantly, the abscopal effect was shown to be tumor specific, because growth of a nonirradiated A20 lymphoma in the same mice containing a treated 67NR tumor was not affected. Moreover, no growth delay of nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were treated with RT plus Flt3-L.Conclusions: These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation. (C) 2004 Elsevier Inc.