Pan Yu, Fei Qinglin, Xiong Ping, Yang Jianyang, Zhang Zheyang, Lin Xianchao, Pan Minggui, Lu Fengchun, Huang Heguang
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
Department of obstetrics and gynecology, 900 Hospital of the Joint Logistics Team, Fuzhou, China.
Oncoimmunology. 2019 Mar 1;8(5):e1581529. doi: 10.1080/2162402X.2019.1581529. eCollection 2019.
Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation between the expression of PD-L1 and c-Myc. Moreover, the expression of both PD-L1 and c-Myc was associated with poor overall survival. In addition, we confirmed this finding with the PDAC patients in the TCGA database. Using several PDAC cell lines we demonstrated a significant correlation between the expression of PD-L1 and c-Myc. We also found that expression of PD-L1 correlated with high-grade histology. JQ1, an inhibitor of c-Myc inhibited PD-L1 expression and tumor growth. Using xenograft models, we demonstrated that the combination of JQ1 and anti-PD-L1 antibody exerted synergistic inhibition of PDAC growth. Our data demonstrated that the expression of PD-L1 and c-Myc may be helpful prognostic biomarkers, and their inhibition may potentially serve as an effective treatment for PDAC.
人类胰腺导管腺癌（PDAC）对抗PD-1/PD-L1免疫疗法反应甚微，其机制仍知之甚少。我们研究了抗PD-L1和c-Myc抑制在PDAC中的作用。利用我院数据库中的87例PDAC患者，我们发现PD-L1和c-Myc的表达之间存在显著相关性。此外，PD-L1和c-Myc的表达均与总生存期较差有关。此外，我们在TCGA数据库中的PDAC患者中证实了这一发现。使用几种PDAC细胞系，我们证明了PD-L1和c-Myc的表达之间存在显著相关性。我们还发现PD-L1的表达与高级别组织学相关。JQ1，一种c-Myc抑制剂，可抑制PD-L1表达和肿瘤生长。使用异种移植模型，我们证明JQ1和抗PD-L1抗体联合使用对PDAC生长具有协同抑制作用。我们的数据表明，PD-L1和c-Myc的表达可能是有用的预后生物标志物，对它们的抑制可能有望成为PDAC的有效治疗方法。
