Inflammasomes in cancer: a double-edged sword

Abstract

Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

“…36 The inflammasome complex promotes inflammatory cell death through activation of cysteine protease caspase-1 and is purported to have tumor suppressive effects in some studies. 37 Our finding of upregulated GBP1, GBP4, and GBP5 in medullary carcinoma compared with all other colorectal carcinomas including microsatellite unstable colorectal carcinomas suggests a possible mechanistic link between the pro-inflammatory microenvironment and observed more favorable clinical outcomes in microsatellite unstable colorectal carcinomas.…”

Cell-Cell Communication in the Tumor Microenvironment, Carcinogenesis, and Anticancer Treatment

“…The authors also showed that ATP-release through Pannexin-1 channels of dying autophagic cells, P(2)X(7) purinergic receptor activation, and a functional K + -channel with potassium efflux are all necessary participants in activating inflammasome. Inflammasomes can be a double-edged sword in cancer [240]. …”

Modulators affecting the immune dialogue between human immune and colon cancer cells

“…Inflammasomes are closely related to chronic inflammation since they act as activators of IL-1β and IL-18 release by PBMC [22,23] . Moreover, activation of inflammasomes may stimulate cancer development [24] . The ability of PBMC to produce inflammatory cytokines plays a major role in the modulation of chronic inflammatory responses associated with carcinogenesis.…”