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Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1

Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 ONCOIMMUNOLOGY Pan, Y., Fei, Q., Xiong, P., Yang, J., Zhang, Z., Lin, X., Pan, M., Lu, F., Huang, H. 2019; 8 (5): e1581529

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.

View details for DOI 10.1080/2162402X.2019.1581529

View details for Web of Science ID 000463705600003

View details for PubMedID 31069140

View details for PubMedCentralID PMC6492971