-PD-L1 mAb enhances the abscopal effect of hypo-fractionated radiation by attenuating PD-L1 expression and inducing CD8(+) T-cell infiltration

作者：Wang, Hui; Lin, Xiangjie; Luo, Yuan; Sun, Shaoxing; Tian, Xiaoli; Sun, Yingming; Zhang, Shimin; Chen, Jing; Zhang, Junhong; Liu, Xuefeng; Liu, Huan; Gong, Yan; Xie, Conghua^*

来源：Immunotherapy, 2019, 11(2): 101-118.

DOI：10.2217/imt-2018-0049

• abscopal effect
• checkpoint immunotherapy
• cytokine
• IFN-
• radiotherapy

Aim: We investigated a promising cooperative combination of radiotherapy (RT) and programmed death ligand 1 (PD-L1) monoclonal antibodies (mAb) in both local and abscopal tumors. Materials & methods: C57BL/6 mice were randomly grouped and received RT, -PD-L1 mAb or combination therapy 13 days after implantation of Lewis lung carcinoma cells. Flow cytometry and immunohistochemistry analyses demonstrated CD8(+) T-cell infiltration and PD-L1 expression in tumor issue. Cytometric bead arrays were used to examine cytokine levels. Results: Our studies revealed that administration of 8 Gyx3 F with -PD-L1 mAb promoted both local and distant control. Only local hypofractionated RT enhanced CD8(+) T-cell infiltration with increased PD-L1 expression at distant foci, which might occur via serum IFN- modulation. Addition of -PD-L1 mAb reduced PD-L1 expression and further increased CD8(+) T-cell infiltration. Conclusion: We identified a novel mechanism through which combination therapy enhanced the abscopal effect.

• 出版日期2019-2
• 单位武汉大学