PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer.

Autor: Mimura K; Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan.; Department of Advanced Cancer Immunotherapy, Fukushima Medical University, Fukushima, Japan.; Department of Progressive DOHaD Research, Fukushima Medical University, Fukushima, Japan., Teh JL; Department of Surgery, National University Health System, Singapore, Singapore., Okayama H; Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan., Shiraishi K; First Department of Surgery, University of Yamanashi, Yamanashi, Japan., Kua LF; National University Cancer Institute Singapore, National University Health System, Singapore, Singapore., Koh V; National University Cancer Institute Singapore, National University Health System, Singapore, Singapore., Smoot DT; Department of Internal Medicine, Meharry Medical College, Nashville, TN, USA., Ashktorab H; Department of Medicine and Cancer Center, Howard University, Washington, DC, USA., Oike T; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan., Suzuki Y; Department of Radiation Oncology, Fukushima Medical University, Fukushima, Japan., Fazreen Z; Cancer Science Institute of Singapore, Singapore, Singapore., Asuncion BR; Cancer Science Institute of Singapore, Singapore, Singapore., Shabbir A; National University Cancer Institute Singapore, National University Health System, Singapore, Singapore., Yong WP; National University Cancer Institute Singapore, National University Health System, Singapore, Singapore., So J; National University Cancer Institute Singapore, National University Health System, Singapore, Singapore., Soong R; Cancer Science Institute of Singapore, Singapore, Singapore.; Department of Pathology, National University of Singapore, Singapore, Singapore., Kono K; Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2018 Jan; Vol. 109 (1), pp. 43-53. Date of Electronic Publication: 2017 Nov 18.
DOI: 10.1111/cas.13424
Abstrakt: 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 vitro setting and in clinical samples. Our in vitro 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.)
Databáze: MEDLINE
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