Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1. (4th May 2019)

• Record Type: Journal Article
• Authors: Pan, Yu; Fei, Qinglin; Xiong, Ping; Yang, Jianyang; Zhang, Zheyang; Lin, Xianchao; Pan, Minggui; Lu, Fengchun; Huang, Heguang
• Is Part Of: Oncoimmunology. Volume 8:Number 5(2019)
• Publication Date: 2019-05-04
• Subjects: C-Myc -- PD-L1 -- JQ1 -- immunotherapy -- pancreatic cancer; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1581529
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.