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|Title:||PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer||Authors:||Mimura K.
|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. https://doi.org/10.1111/cas.13424||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||URI:||http://scholarbank.nus.edu.sg/handle/10635/146666||ISSN:||13479032||DOI:||10.1111/cas.13424|
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