Abstract
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.
Original language | English (US) |
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Pages (from-to) | 634-648.e5 |
Journal | Cancer cell |
Volume | 33 |
Issue number | 4 |
DOIs | |
State | Published - Apr 9 2018 |
Keywords
- IL-18
- cancer
- immunosuppression
- immunotherapy
- inflammasome
- inflammation
- myeloid-derived suppressor cells
- myeloma
- tumor microenvironment
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research