Abstract 615: Local irradiation with systemic anti-PD1 antibody may effectively suppress the micrometastasis in distant organ through the induction of abscopal effects
Authors: Hidenori Tsukui, Rihito Kanamaru, Ai Sadatomo, Daishi Naoi, Tetsuichiro Shimizu, Makiko Tahara, Katsusuke Mori, Homare Ito, Mitsuaki Morimoto, Yoshihiko Kono, Yoshiyuki Inoue, Hiroyuki Maruyama, Koji Koinuma, Hisanaga Horie, Yasunaru Sakuma, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama
Journal: Cancer Research (2017)

Abstract Background: Tumor shrinkage in response to radiotherapy (RT) is partially dependent on host immunity. Recent clinical results have suggested that PD-1/PD-L1 blockade markedly augments the antitumor immune response especially in case of numerous genetic mutations. Here, in this study, we evaluated if anti-PD-1 mAb can induce abscopal effects of local RT in murine model. Method: Murine colon cancer cell, LuM-1, is a highly metastatic clone of colon 26. After subcutaneous (s.c) inoculation of LuM-1, micro- and macro- metastases were observed in bilateral lung at 1 and 2 weeks, respectively. Then, LuM-1 (2×105 per mouse) was s.c implanted subcutaneously in the left flanks of BALB/c mice. At day 8, mice were divided into 4 (control, RT, anti-PD-1 mAb, RT+anti-PD-1 mA) groups with each group containing 5 mice. In RT group, mice received local RT at day 9 and 17. In brief, anesthetized mice were held in the decubitus position, with the whole body except left flank tumor protected by a lead shield and the ionizing irradiation (X-ray, 8Gy) was selectively delivered to s.c. tumor using MBR-1505R2 (Hitachi Medical Co.) Anti-PD-1 mAb (J43) or control hamster mAb (0.5mg) was given at day 9,11,13 and 17,19,21 At day 28, mice were sacrificed and s.c tumor and lung metastases were quantified with tumor size and lung weight, respectively. Results: S.c tumor was significantly reduced by RT and/or PD-1 mAb with additive effects. The whole lung weight in PD-1 mAb group was 120±64.0 gr, which was significantly less than control mAb group (306±38.4 gr, p&amp;lt;0.05) RT alone did not affect the lung weight (298±40.0 gr), however, RT if combined withPD-1 mAb, tended to further reduce the lung metastases (69.0±31.5gr,. p=0.12). Conclusion: Local RT and PD-1 mAb is effective to prevent the growth of micrometastasis in non-irradiated sites through the augmentation of abscopal effects. Combination of RT and immune checkpoint inhibitors can be a new treatment strategy for locally advanced rectal cancer. Citation Format: Hidenori Tsukui, Rihito Kanamaru, Ai Sadatomo, Daishi Naoi, Tetsuichiro Shimizu, Makiko Tahara, Katsusuke Mori, Homare Ito, Mitsuaki Morimoto, Yoshihiko Kono, Yoshiyuki Inoue, Hiroyuki Maruyama, Koji Koinuma, Hisanaga Horie, Yasunaru Sakuma, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama. Local irradiation with systemic anti-PD1 antibody may effectively suppress the micrometastasis in distant organ through the induction of abscopal effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 615. doi:10.1158/1538-7445.AM2017-615