Inflammasomes and Cancer

Abstract

Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat containing proteins (NLRs), AIM2-like receptors (ALRs), or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6 and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL-18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL-1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this Review, we explore the crossroads between inflammasomes and the development of various tumors, and discuss possible therapeutic values in targeting the inflammasome for the prevention and treatment of cancer.

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

“…In other models, however, NLRP3 null mice had reduced lung metastasis with B16-F10 tumor cells (46). These examples highlight the complex association between the inflammasome complex and cancer, which were have been reviewed in detail (47)(48)(49).…”

Colorectal Cancer and NLRP-Current Knowledge

“…Inflammation is orchestrated by the inflammasome in many cells (immune, epithel, cancer) [1]. The NLRP3 inflammasome is the most known inflammasome.…”

“…The NLRP3 inflammasome is the most known inflammasome. It is a multiprotein citoplasmic complex activated by pathogen-associated molecular patterns (PAMPs) (such as bacterial and viral nucleic acid), damage-associated molecular patterns (DAMPs) (for example, ATP and uric acid crystals) or environmental irritans [1][2][3].…”

“…Different stimuli activate different inflammasomes and mediate many important processes in CLC [3,6]. NLRP1-β, NLRP3, and NLRP6's activation of caspase-1 results in maturation of proinflammatory cytokine interleukin (IL)-1β and IL-18 and pyroptosis [1,7].…”

“…IL-1β suppresses NK and T cells activity against tumor [1]. Its level increases during the progression of CRC.…”