Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the
world. Inflammation is often an underlying risk factor for developing CRC. Maintaining
gut homeostasis and balancing inflammation is therefore critical to prevent CRC development.
One key class of molecular complexes that impact gut homeostasis are inflammasomes,
cytosolic multiprotein immune complexes that assemble upon sensing various intracellular
alterations. Inflammasomes regulate inflammation, cell death, cytokine release, signaling
cascades, and other cellular processes. Roles for inflammasomes in colitis and colitis-associated
CRC have been shown in multiple animal models. The activation of inflammasomes leads
to the release of the bioactive forms of interleukin (IL)-1β and IL-18, the inflammasome
effector cytokines. These cytokines ensure an optimal inflammatory immune response
during colitis and colitis-associated CRC. The activation of some inflammasome sensors,
including NLRP3, NLRP1, NLRP6, and Pyrin, provides protection from colitis-associated
CRC via effector cytokine-dependent mechanisms. Additionally, activation of other
inflammasome sensors, such as AIM2, NLRC4, and NAIPs, provides mostly effector cytokine-independent
protection. Inflammasomes can also act as integral components of PANoptosomes, which
are multifaceted complexes that integrate components from other cell death pathways
and regulate a unique form of innate immune inflammatory cell death called PANoptosis.
Furthermore, IRF1, a key regulator of some inflammasomes and PANoptosomes, has been
implicated in CRC. It is therefore critical to consider the role of inflammasomes
in effector cytokine-dependent and -independent protection as well as their role in
PANoptosis to modulate CRC for therapeutic targeting. Here, we discuss the mechanisms
of inflammasome activation, the functions of inflammasomes in CRC, and current obstacles
and future perspectives in inflammasome and CRC research.
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Article info
Publication history
Published online: September 20, 2022
Accepted:
September 15,
2022
Received in revised form:
August 29,
2022
Received:
July 15,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
