Please use this identifier to cite or link to this item:
Title: PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer
Authors: Mimura K.
Teh J.L.
Okayama H.
Shiraishi K.
Kua L.-F.
Koh V.
Smoot D.T.
Ashktorab H.
Oike T.
Suzuki Y.
Fazreen Z.
Asuncion B.R.
Shabbir A. 
Yong W.-P.
So J. 
Soong R. 
Kono K.
Keywords: CD8
gastric cancer
Issue Date: 1-Jan-2018
Publisher: Blackwell Publishing Ltd
Citation: Mimura K., Teh J.L., Okayama H., Shiraishi K., Kua L.-F., Koh V., Smoot D.T., Ashktorab H., Oike T., Suzuki Y., Fazreen Z., Asuncion B.R., Shabbir A., Yong W.-P., So J., Soong R., Kono K. (2018-01-01). PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer. Cancer Science 109 (1) : 43-53. ScholarBank@NUS Repository.
Abstract: Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in an in爒itro setting and in clinical samples. Our in爒itro findings showed that interferon gamma upregulated programmed death ligand-1 expression on solid tumor cells through the JAK-signal transducer and activator of transcription pathway, and impaired the cytotoxicity of tumor antigen-specific CTL against tumor cells. Following treatment of cells with anti-programmed death ligand-1 mAb after interferon gamma-pre-treatment, the reduced anti-tumor CTL activity by interferon gamma reached a higher level than the non-treatment control targets. In contrast, programmed death ligand-1 expression on tumor cells also significantly correlated with epithelial-mesenchymal transition phenotype in a panel of solid tumor cells. In clinical gastric cancer samples, tumor membrane programmed death ligand-1 expression significantly positively correlated with the presence of CD8-positive T cells in the stroma and interferon gamma expression in the tumor. The results suggest that gastric cancer patients with high CD8-positive T-cell infiltration may be more responsive to anti-programmed death 1/-programmed death ligand-1 mAb therapy. � 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Source Title: Cancer Science
ISSN: 13479032
DOI: 10.1111/cas.13424
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
cas.13424.pdf1.51 MBAdobe PDF




checked on Aug 19, 2019


checked on Jul 17, 2019

Page view(s)

checked on Aug 15, 2019


checked on Aug 15, 2019

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.