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 Vk∗MYC 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.
Pubmed ID: 29551594 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Collection of pathways and pathway annotations. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways (signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism) . Provides website to navigate pathway knowledge and a suite of data analysis tools to support the pathway-based analysis of complex experimental and computational data sets.
View all literature mentionsThis unknown targets Mouse Rat Asialo GM1
View all literature mentionsThis monoclonal targets Ly6G
View all literature mentionsThis monoclonal targets CD8β (Lyt 3.2)
View all literature mentionsThis monoclonal targets CD3epsilon
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD33
View all literature mentionsThis monoclonal targets HLA-DR
View all literature mentionsThis monoclonal targets CD11b/Mac-1
View all literature mentionsThis monoclonal targets CD8
View all literature mentionsThis monoclonal targets Human CD4
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets ARG1
View all literature mentionsThis monoclonal targets NOS2
View all literature mentionsThis polyclonal targets CEBPB
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets TCR beta chain
View all literature mentionsThis monoclonal targets CD138
View all literature mentionsThis monoclonal targets CD138
View all literature mentionsThis monoclonal targets CD45R
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentions