Baba Kiichiro, Nomura Motoo, Ohashi Shinya, Hiratsuka Takuya, Nakai Yukie, Saito Tomoki, Kondo Yuki, Fukuyama Keita, Kikuchi Osamu, Yamada Atsushi, Matsubara Junichi, Hirohashi Kenshiro, Mitani Yosuke, Mizumoto Ayaka, Muto Manabu
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.
Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.
Am J Cancer Res. 2020 Feb 1;10(2):440-453. eCollection 2020.
Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT.
放射疗法(RT)是癌症的主要治疗方法。RT产生的电离辐射会在照射部位引发肿瘤损伤,并且,尽管在临床上并不常见,但可能会导致远离照射部位的肿瘤消退——这一现象被称为远隔效应。最近,远隔效应与癌症患者总生存时间的延长有关,不过影响远隔效应的因素尚未完全明确。本研究的目的是阐明影响远隔效应的因素。在此,我们建立了一个能够诱导远隔效应的小鼠模型。我们在两个部位将MC38(小鼠结肠腺癌)细胞皮下注射到C57BL/6小鼠体内。仅对其中一个肿瘤进行照射,并随时间测量两个肿瘤的大小。未照射部位的肿瘤出现消退,证实了远隔效应。照射肿瘤体积的增加以及抗PD1抗体的给药可增强这种效应。当通过RT与抗PD1抗体联合诱导远隔效应时,它还受辐射剂量和照射肿瘤体积的影响。这些现象在其他细胞系B16F10细胞(小鼠黑色素瘤细胞)中也得到了验证。这些发现为RT中远隔效应的机制及影响因素提供了进一步的证据。