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, 2018 04 09.
Article
em En
| MEDLINE
| ID: mdl-29551594
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.
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Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
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Linfócitos T CD8-Positivos
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Interleucina-18
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Células Supressoras Mieloides
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Mieloma Múltiplo
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article