Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment.
Fiche publication
Date publication
avril 2018
Journal
Cancer cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHRETIEN Marie-Lorraine
Tous les auteurs :
Nakamura K, Kassem S, Cleynen A, Chrétien ML, Guillerey C, Putz EM, Bald T, Förster I, Vuckovic S, Hill GR, Masters SL, Chesi M, Bergsagel PL, Avet-Loiseau H, Martinet L, Smyth MJ
Lien Pubmed
Résumé
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from VkMYC MM progression in a CD8 T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses. Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM.
Mots clés
IL-18, cancer, immunosuppression, immunotherapy, inflammasome, inflammation, myeloid-derived suppressor cells, myeloma, tumor microenvironment
Référence
Cancer Cell. 2018 04 9;33(4):634-648.e5