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

Yu Pan; Qinglin Fei; Ping Xiong; Jianyang Yang; Zheyang Zhang; Xianchao Lin; Minggui Pan; Fengchun Lu; Heguang Huang

doi:10.1080/2162402X.2019.1581529

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

Oncoimmunology. 2019 Mar 1;8(5):e1581529. doi: 10.1080/2162402X.2019.1581529. eCollection 2019.

Authors

Yu Pan¹, Qinglin Fei¹, Ping Xiong², Jianyang Yang¹, Zheyang Zhang³, Xianchao Lin¹, Minggui Pan⁴, Fengchun Lu¹, Heguang Huang¹

Affiliations

¹ Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
² Department of obstetrics and gynecology, 900 Hospital of the Joint Logistics Team, Fuzhou, China.
³ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
⁴ Department of Oncology and Hematology and Division of Research, Kaiser Permanente, Santa Clara, CA, USA.

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.

Keywords: C-Myc; JQ1; PD-L1; immunotherapy; pancreatic cancer.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This study was supported by the Medical Talents Training Program of Health and Family Planning Commission of Fujian Province (2016-ZQN-34); The Medical Center of Minimally Invasive Technology of Fujian Province (No. 171, 2017 and No. 4, 2017); Joint Funds of Scientific and Technological Innovation Program of Fujian Province (2017Y9059);Joint Funds of Scientific and Technological Innovation Program of Fujian Province [2017Y9059];The Medical Center of Minimally Invasive Technology of Fujian Province [No. 171, 2017 and No. 4, 2017].