| Literature DB >> 30374200 |
Michaël Cerezo1,2, Ramdane Guemiri1,2,3,4,5, Sabine Druillennec5,6,7, Isabelle Girault1,2, Hélène Malka-Mahieu3,4,5, Shensi Shen1,2, Delphine Allard1,2, Sylvain Martineau3,4,5, Caroline Welsch1,2,3,4,5, Sandrine Agoussi1,2, Charlène Estrada5,6,7, Julien Adam1,8, Cristina Libenciuc9, Emilie Routier9, Séverine Roy9, Laurent Désaubry10, Alexander M Eggermont2,9, Nahum Sonenberg11, Jean Yves Scoazec8, Alain Eychène5,6,7, Stéphan Vagner12,13,14,15, Caroline Robert16,17,18.
Abstract
Preventing the immune escape of tumor cells by blocking inhibitory checkpoints, such as the interaction between programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) receptor, is a powerful anticancer approach. However, many patients do not respond to checkpoint blockade. Tumor PD-L1 expression is a potential efficacy biomarker, but the complex mechanisms underlying its regulation are not completely understood. Here, we show that the eukaryotic translation initiation complex, eIF4F, which binds the 5' cap of mRNAs, regulates the surface expression of interferon-γ-induced PD-L1 on cancer cells by regulating translation of the mRNA encoding the signal transducer and activator of transcription 1 (STAT1) transcription factor. eIF4F complex formation correlates with response to immunotherapy in human melanoma. Pharmacological inhibition of eIF4A, the RNA helicase component of eIF4F, elicits powerful antitumor immune-mediated effects via PD-L1 downregulation. Thus, eIF4A inhibitors, in development as anticancer drugs, may also act as cancer immunotherapies.Entities:
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Year: 2018 PMID： 30374200 DOI： 10.1038/s41591-018-0217-1
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440