Abstract
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 regulatory mechanisms underlying its regulation are not completely understood. Here, we show that the eIF4F eukaryotic translation initiation complex, which binds the 5’ cap of mRNAs, regulates the surface expression of interferon-induced PD-L1 on cancer cells by regulating translation of the mRNA encoding the STAT1 transcription factor. eIF4F complex formation correlates with response to immunotherapy in human melanoma. Pharmacologic 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 anti-ancer drugs, may also act as cancer immunotherapies. Citation Format: Michael Cerezo, Ramdane Guemiri, Isabelle Girault, Caroline Robert, Stephan Vagner. Translational control of tumor immune escape via the eIF4F-STAT1-PDL1 axis in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B40.
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