The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines
Autor: | Kazuhiko Uchiyama, Kazuhiro Kamada, Yuji Naito, Tomoyo Yasuda, Takeshi Ishikawa, Kazuhiro Katada, Toshifumi Doi, Naoyuki Sakamoto, Katsura Mizushima, Kaname Oka, Tetsuya Okayama, Yoshito Itoh, Tomohisa Takagi, Osamu Handa |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Blotting Western Antineoplastic Agents Apoptosis Biology Real-Time Polymerase Chain Reaction B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Downregulation and upregulation Pancreatic cancer medicine Tumor Cells Cultured Humans RNA Messenger Cell Proliferation Oncogene Reverse Transcriptase Polymerase Chain Reaction JAK-STAT signaling pathway General Medicine Immunotherapy Cell cycle Janus Kinase 2 medicine.disease Flow Cytometry Gemcitabine Gene Expression Regulation Neoplastic Pancreatic Neoplasms 030104 developmental biology STAT1 Transcription Factor Oncology 030220 oncology & carcinogenesis Cancer research medicine.drug Signal Transduction |
Zdroj: | Oncology reports. 37(3) |
ISSN: | 1791-2431 |
Popis: | 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. |
Databáze: | OpenAIRE |
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