PD-L1 expression is regulated by both DNA methylation and NF-kB during EMT signaling in non-small cell lung carcinoma.
Fiche publication
Date publication
janvier 2018
Journal
Oncoimmunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Pr GUITTAUT Michaël, Dr GODET Yann, Dr HERVOUET Eric, Dr PEIXOTO Paul, Mme BOUARD Adeline, Dr GUENAT David, Dr ASGAROV Kamal, Dr GALAINE Jeanne
Tous les auteurs :
Asgarova A, Asgarov K, Godet Y, Peixoto P, Nadaradjane A, Boyer-Guittaut M, Galaine J, Guenat D, Mougey V, Perrard J, Pallandre JR, Bouard A, Balland J, Tirole C, Adotevi O, Hendrick E, Herfs M, Cartron PF, Borg C, Hervouet E
Lien Pubmed
Résumé
Tumor cells, which undergo Epithelial-mesenchymal transition (EMT) acquire increased capacities of proliferation, invasion and have the ability to generate metastases by escaping the immune system during their systemic migration. To escape the immune system, cancer cells may induce tolerance or resist elimination by immune effectors multiple mechanisms and we hypothesized that EMT may control the expression of immune checkpoint inhibitors, then promoting immune evasion. PD-L1 (programmed cell death ligand 1) but not PD-L2 nor Galectin 9 or Death receptor (DR4, DR5 and Fas) and ligands (FasL and TRAIL) expression was up-regulated during cytokine-driven EMT in a reversible manner. Moreover PD-L1 is overexpressed in VIMENTIN positive NSCLC tissues. We also demonstrated that the expression of PD-L1 required both TNFα and TGFβ1. Indeed, TGFβ1 decreased DNMT1 content and that resulted in promoter demethylation whereas TNFα induced the NF-κB pathway that promoted expression of demethylated promoter.
Mots clés
DNA methylation, NF-kB, PD-L1, death receptors, epithelial-mesenchymal transition, lung cancer, cancer
Référence
Oncoimmunology. 2018 ;7(5):e1423170