| RRC ID |
52072
|
| 著者 |
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.
|
| タイトル |
The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines.
|
| ジャーナル |
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.
|
| 巻・号 |
37(3)
|
| ページ |
1545-1554
|
| 公開日 |
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 |
3.417
|
| 引用数 |
39
|
| リソース情報 |
| ヒト・動物細胞 |
MIA Paca2(RCB2094) |
