Translational control of tumor immune escape via the eIF4F–STAT1–PD-L1 axis in melanoma (Nat Med. 2018, 24(12):1877-1886)

報告日期: 2019/04/12
報告時間: 16:00/16:50
報告學生: 李忠諺(以英文報告)
講評老師: 林世杰
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Translational control of tumor immune escape via

the eIF4F–STAT1–PD-L1 axis in melanoma

Michaël Cerezo, Ramdane Guemiri, Sabine Druillennec, Caroline Robert

Nature medicine (2018)

Presenter: Chung-Yen Li

Coordinator: Prof. Chia-Yih Wang           Date/Time: 2019/04/12 16:10-17:00

Commentator: Prof. Shih-Chieh Lin. Location: Room 602, Med. College Building

Abstract

Anti–programmed cell death protein 1 (PD-1) immunotherapy had been exceedingly effective in activating T cell responses to cancer. However, only 20% of patients had a response to this treatment [1]. Tumor PD-L1 expression was an important biomarker for anti PD-1/PD-L1 treatment, but its regulation mechanisms were not fully understood. In this study, the authors found that eukaryotic translation initiation factor 4F, which was composed by eIF4E, eIF4A, and eIF4G, regulated interferon-gamma- induced PD-L1 expression on cell surface in most cancer cell lines. In addition, eIF4F complex formation was positive correlation with PD-L1 expression in the melanoma patients. Moreover, the authors found that eIF4F regulated the PD-L1 expression through STAT1 regulation by microarray analysis of polysomal mRNAs. Pharmacological inhibition of eIF4A, the RNA helicase component of eIF4F, increased the antitumor effect and reduced the expression of PD-L1 in the mouse model. These findings suggest that eIF4A inhibitor may develop to a cancer immunotherapy drug 

  1. Topalian, S.L., C.G. Drake, and D.M. Pardoll, Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell, 2015. 27(4): p. 450-61.