Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade
Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade
复制标题
阻断 C5aR 信号传导可促进 PD-1/PD-L1 阻断的抗肿瘤功效
DOI：
10.1080/2162402x.2017.1349587
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发表时间：
2017
期刊：
影响因子：
7.2
通讯作者：
Zhu Bo
中科院分区：
文献类型：
--
作者：
Zha Haoran;Han Xiao;Zhu Ying;Yang Fei;Li Yongsheng;Li Qijing;Guo Bo;Zhu Bo
抗pd -1/PD-L1治疗在临床上取得了巨大成功；然而，只有一小部分癌症患者受益于PD-1/PD-L1阻断治疗，因此克服对PD-1/PD-L1阻断的耐药成为当务之急。在这项研究中，我们证明了PD-1/PD-L1抗体的使用导致补体系统的激活和C5a的大量产生。C5a的产生并未改变MDSCs在肿瘤或脾脏中的积累，但增强了它们的抑制潜能。此外，阻断C5a-C5aR信号并联合PD-1/PD-L1抗体可大大增强PD-1/PD-L1抗体的抗肿瘤效果。总的来说，这些数据表明C5a在PD-1/PD-L1阻断治疗中具有免疫抑制作用，并为临床探索使用C5a拮抗剂的联合治疗提供了强大的动力。
Anti-PD-1/PD-L1 therapy has achieved great success in the clinic; however, only a small fraction of cancer patient benefit from PD-1/PD-L1 blockade therapy, and overcoming resistance to PD-1/PD-L1 blockade has thus become a primary priority. In this study, we demonstrated that administration of PD-1/PD-L1 antibodies resulted in the activation of the complement system and massive generation of C5a. Generation of C5a did not change the accumulation of MDSCs in either the tumor or spleen but enhanced their inhibitory potential. In addition, blockade of C5a-C5aR signaling in combination with PD-1/PD-L1 antibodies greatly enhanced the anti-tumor efficacy of PD-1/PD-L1 antibodies. Overall, these data indicate an immunosuppressive role of C5a in the context of PD-1/PD-L1 blockade therapy and provide a strong incentive to clinically explore combination therapies using a C5a antagonist.