IFN gamma induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma
- Authors
- Moon, Ji Wook; Kong, Su Kang; Kim, Byung Soo; Kim, Hyun Ji; Lim, Hyangsoon; Noh, Kyeonga; Kim, Younghye; Choi, Jung-Woo; Lee, Ju-Han; Kim, Young-Sik
- Issue Date
- Dec-2017
- Publisher
- Nature Publishing Group
- Citation
- Scientific Reports, v.7
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Scientific Reports
- Volume
- 7
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4331
- DOI
- 10.1038/s41598-017-18132-0
- ISSN
- 2045-2322
- Abstract
- Programmed death-ligand1 (PD-L1) acts as an immune checkpoint inhibitor in various cancers. PD-L1 is known to be more frequently expressed in EBV (+) gastric cancer (GC). However, the mechanisms underlying the regulation of PD-L1 expression in EBV (+) GC remain unclear. We investigated the basal and inducible PD-L1 expressions in GC cells. PD-L1 expression was upregulated upon treatment with IFN gamma in both EBV (-) and EBV (+) GC cells. Upon stimulation with the same concentration of IFN gamma for 24 h, EBV (+) SNU-719 cells showed dramatically higher PD-L1 expression levels by activating JAK2/STAT1/IRF-1 signaling than those of EBV (-) AGS cells. PD-L1 promoter assays, chromatin immunoprecipitation, and electrophoretic mobility shift assays revealed that IFN gamma-inducible PD-L1 overexpression is primarily mediated by the putative IRF-1 alpha site of the PD-L1 promoter in EBV (+) SNU-719 cells. Moreover, EBNA1 knockdown reduced both constitutive and IFN gamma-inducible PD-L1 promoter activity by decreasing the transcript and protein levels of JAK2 and subsequently STAT1/IRF-1/PD-L1 signaling. EBNA1 is suggested to be moderately enhance both constitutive and IFN gamma-inducible PD-L1 expression in EBV (+)GC cells. Thus, the signaling proteins and EBNA1 that regulate PD-L1 expression are potential therapeutic targets in EBV (+) GC.
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- Appears in
Collections - 2. Clinical Science > Department of Pathology > 1. Journal Articles
- 1. Basic Science > Department of Pathology > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
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