2019年1月
PD-L1 expression enhancement by infiltrating macrophage-derived tumor necrosis factor-α leads to poor pancreatic cancer prognosis.
Cancer science
- 巻
- 110
- 号
- 1
- 開始ページ
- 310
- 終了ページ
- 320
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/cas.13874
- 出版者・発行元
- WILEY
Immunotherapy using anti-PD-1/PD-L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD-L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD-L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)-α upregulated PD-L1 expression in PDAC cells through NF-κB signaling. The induction of PD-L1 expression was also caused by co-culture with activated macrophages, and the upregulation was inhibited by neutralization with anti-TNF-α antibody after co-culture with activated macrophages. PD-L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD-L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8-positive T-cell infiltration. These findings indicate that tumor-infiltrating macrophage-derived TNF-α could be a potential therapeutic target for PDAC.
- リンク情報
-
- DOI
- https://doi.org/10.1111/cas.13874
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/30426611
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317925
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000454938300028&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1111/cas.13874
- ISSN : 1347-9032
- eISSN : 1349-7006
- PubMed ID : 30426611
- PubMed Central 記事ID : PMC6317925
- Web of Science ID : WOS:000454938300028