RRC ID 52072
Author Doi T, Ishikawa T, Okayama T, Oka K, Mizushima K, Yasuda T, Sakamoto N, Katada K, Kamada K, Uchiyama K, Handa O, Takagi T, Naito Y, Itoh Y.
Title The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines.
Journal Oncol Rep
Abstract Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02. Additionally, we analyzed the molecular mechanisms that facilitated the regulation of PD-L1 expression in these cell lines. We observed that when AsPC-1, MIA PaCa-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein expression was enhanced. Similarly, the mRNA level of PD-L1 was upregulated in the AsPC-1 and Pan02 cells when stimulated by each of the three anticancer agents. The phosphorylation of STAT1 and an increase in total STAT1 were also observed in the AsPC-1 cells when stimulated by each anticancer agent. In response to JAK2 inhibitor treatment, PD-L1 upregulation induced by the anticancer agents was reduced in a dose-dependent manner. These results suggest that i) the JAK2/STAT1 pathway is involved in the anticancer agent-mediated PD-L1 transcription; and ii) the anticancer agents altered the tumor immune response which may induce tumor immune escape. These findings can have an influence on the design of treatments that combine chemotherapy and immunotherapy.
Volume 37(3)
Pages 1545-1554
Published 2017-3-1
DOI 10.3892/or.2017.5399
PMID 28112370
MeSH Antineoplastic Agents / pharmacology* Apoptosis / drug effects B7-H1 Antigen / genetics B7-H1 Antigen / metabolism* Blotting, Western Cell Proliferation / drug effects Flow Cytometry Gene Expression Regulation, Neoplastic / drug effects* Humans Janus Kinase 2 / genetics Janus Kinase 2 / metabolism* Pancreatic Neoplasms / drug therapy Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / genetics STAT1 Transcription Factor / metabolism* Signal Transduction Tumor Cells, Cultured
IF 3.041
Times Cited 39
Human and Animal Cells MIA Paca2(RCB2094)