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.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Pan Y,Fei Q,Xiong P,Yang J,Zhang Z,Lin X,Pan M,Lu F,Huang Hdoi
10.1080/2162402X.2019.1581529subject
Has Abstractpub_date
2019-03-01 00:00:00pages
e1581529issue
5eissn
2162-4011issn
2162-402Xpii
1581529journal_volume
8pub_type
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