Dysregulated IL-18 Is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment
- 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;
Publication Year 2018, Volume 33, Issue #4, Page 634-648.e5
- Journal Title
- Cancer Cell
- Publication Type
- Journal Article
- 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. Nakamura et al. show that IL-18 produced by the multiple myeloma (MM) niche promotes MM progression in a CD8+ T cell-dependent manner in a mouse model and that IL-18 could be a potential therapeutic target in MM. High levels of bone marrow plasma IL-18 are associated with poor overall survival in MM patients. © 2018 Elsevier Inc.
- Cell Press
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
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Creation Date: 2018-03-19 10:02:52Last Modified: 2018-07-09 03:25:01