胰腺癌
癌症研究
聚ADP核糖聚合酶
联合疗法
体内
肿瘤微环境
癌症
免疫系统
CD8型
免疫检查点
医学
PD-L1
免疫疗法
药理学
作者
Yali Wang,Kun Zheng,Hua Xiong,Yongbiao Huang,Xiuqiong Chen,Yinghui Zhou,Wan Qin,Jinfang Su,Rui Chen,Hong Qiu,Xianglin Yuan,Yihua Wang,Yanmei Zou
标识
DOI:10.3389/fimmu.2021.762989
摘要
Despite recent improvements in treatment modalities, pancreatic cancer remains a highly lethal tumor with mortality rate increasing every year. Poly (ADP-ribose) polymerase (PARP) inhibitors are now used in pancreatic cancer as a breakthrough in targeted therapy. This study focused on whether PARP inhibitors (PARPis) can affect programmed death ligand-1 (PD-L1) expression in pancreatic cancer and whether immune checkpoint inhibitors of PD-L1/programmed death 1 (PD-1) can enhance the anti-tumor effects of PARPis. Here we found that PARPi, pamiparib, up-regulated PD-L1 expression on the surface of pancreatic cancer cells in vitro and in vivo. Mechanistically, pamiparib induced PD-L1 expression via JAK2/STAT3 pathway, at least partially, in pancreatic cancer. Importantly, pamiparib attenuated tumor growth; while co-administration of pamiparib with PD-L1 blockers significantly improved the therapeutic efficacy in vivo compared with monotherapy. Combination therapy resulted in an altered tumor immune microenvironment with a significant increase in windiness of CD8+ T cells, suggesting a potential role of CD8+ T cells in the combination therapy. Together, this study provides evidence for the clinical application of PARPis with anti-PD-L1/PD-1 drugs in the treatment of pancreatic cancer.
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