免疫刺激剂对放疗的效果可以通过免疫检查点阻断的协同作用而得到加强，以作用于放疗肿瘤病变和远处未接受放疗的肿瘤部位。我们的假设是低剂量全身放疗（L-TBI）与低分数放疗（H-RT）和抗程序性细胞死亡蛋白1（aPD-1）检查点阻断相结合，可增强全身免疫反应。我们在BALB/c小鼠的双侧乳腺癌异种移植模型中测试了这种三联疗法（L-TBI + H-RT + aPD-1）的功效。L-TBI剂量为0.1 Gy。用H-RT（8 Gy × 3）治疗原发肿瘤。PD-1单克隆抗体是经腹腔注射的，未接受H-RT的次要肿瘤则进行响应监测。三联疗法明显延缓了原发和次要肿瘤的生长速度，提高了生存率，并减少了肺转移病灶的数量。相对于其他组，它增加了活化树突状细胞和CD8 + T细胞的数量，减少了生长于次要肿瘤微环境中的髓样耗材细胞浸润。因此，L-TBI可能是一种潜在的治疗模式，当结合H-RT和aPD-1时，治疗效果可以得到显著增强。版权所有©2023 Elsevier B.V.。保留所有权利。

Immunostimulatory effects of radiotherapy can be synergistically augmented with immune checkpoint blockade to act both on irradiated tumor lesions and distant, non-irradiated tumor sites. Our hypothesis was that low-dose total body irradiation (L-TBI) combined with hypo-fractionated radiotherapy (H-RT) and anti-programmed cell death protein 1 (aPD-1) checkpoint blockade would enhance the systemic immune response. We tested the efficacy of this triple therapy (L-TBI + H-RT + aPD-1) in BALB/c mice with bilateral breast cancer xenografts. The L-TBI dose was 0.1 Gy. The primary tumor was treated with H-RT (8 Gy × 3). The PD-1 monoclonal antibody was injected intraperitoneally, and the secondary tumors not receiving H-RT were monitored for response. The triple therapy significantly delayed both primary and secondary tumor growths, improved survival rates, and reduced the number of lung metastasis lesions. It increased the activated dendritic and CD8+ T cell populations and reduced the infiltration of myeloid-derived suppressor cells in the secondary tumor microenvironment relative to other groups. Thus, L-TBI could be a potential therapeutic modality, and when combined with H-RT and aPD-1, the therapeutic effect could be enhanced significantly.Copyright © 2023 Elsevier B.V. All rights reserved.