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The influence of chemotherapeutic agents on programmed death- ligand 1 (PD-L1) expression on pancreatic cancer cells
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T. Doi1,2,
T. Ishikawa1,
T. Okayama1 |
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1Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 2Department of Gastroenterology and Hepatology, Japanese Red Cross Kyoto Daiichi Hospital |
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| Immune checkpoint inhibitors (ICI) as single agents are promising for GI cancers and some of them are about to be approved for GI cancers. The next era for ICI is combined therapy with various other therapies including chemotherapy. To develop rational combination strategies, it is necessary to elucidate the influence of chemotherapy on immune checkpoints. In this study, we evaluated the influence of chemotherapeutic agents on PD-L1 expression in human (MIA PaCA-2, AsPC-1) and murine (Pan02) pancreatic cancer cell lines. Additionally, we analyzed the molecular mechanism about the regulation of PD-L1. We observed that when AsPC-1, MIA PaCA-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein and mRNA expression was enhanced. The STAT1 phosphorylation was also observed in AsPC-1 by chemotherapeutic agents stimulation. In response to JAK2 inhibitor, PD-L1 upregulation induced by chemotherapeutic agents reduced in a dose-dependent manner. These results suggest that the JAK/STAT pathway is involved in the chemotherapeutic agents mediated PD-L1 transcription and that chemotherapeutic agents may induce tumor immune escape. Additionally, we will briefly review recent findings regarding the chemotherapeutic agents-induced PD-L1 regulation. |
Index Term 1: programmed death- ligand 1 (PD-L1）
Index Term 2: JAK/STAT |
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