Diverging inflammasome signals in tumorigenesis and potential targeting

Abstract

Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase 1, thereby promoting the secretion of bioactive interleukin-1 beta (IL-1 beta) and IL-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signalling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis and metastasis. Conversely, inflammasome signalling also contributes to tumour suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the importance of environmental factors, such as diet and gut microbiota, in inflammasome signalling, which in turn influences tumorigenesis. In this Review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as therapeutic targets.