| First Author | Nakamura K | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 4 | Pages | 634-648.e5 |
| PubMed ID | 29551594 | Mgi Jnum | J:260703 |
| Mgi Id | MGI:6151039 | Doi | 10.1016/j.ccell.2018.02.007 |
| Citation | Nakamura K, et al. (2018) Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment. Cancer Cell 33(4):634-648.e5 |
| abstractText | 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. |
