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Review
. 2022 Jun 27;14(13):3150.
doi: 10.3390/cancers14133150.

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

Stavros P Papadakos  1 , Nikolaos Dedes  1 , Elias Kouroumalis  2 , Stamatios Theocharis  1
Affiliations
Review

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

Stavros P Papadakos et al. Cancers (Basel). .

Abstract

The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances in systemic therapy and surgery. This trend is fueled by the rise of an obesity wave which is prominent the Western populations and has reshaped the etiologic landscape of HCC. Interest in the nucleotide-binding domain leucine-rich repeat containing (NLR) family member NLRP3 has recently been revived since it would appear that, by generating inflammasomes, it participates in several physiologic processes and its dysfunction leads to disease. The NLRP3 inflammasome has been studied in depth, and its influence in HCC pathogenesis has been extensively documented during the past quinquennial. Since inflammation comprises a major regulator of carcinogenesis, it is of paramount importance an attempt to evaluate the contribution of the NLRP3 inflammasome to the generation and management of HCC. The aim of this review was to examine the literature in order to determine the impact of the NLRP3 inflammasome on, and present a hypothesis about its input in, HCC.

Keywords: HCC; NLRP3; inflammasome; innate immunity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
On the left is presented the activation of the NLRP3 inflammasome. PAMPs and DAMPs from the neighboring parenchyma stimulate the PRR system to upregulate the expression of NF-kB (Signal 1—priming), which triggers the expression of pro-ILs and the components of the inflammasome machinery. Additional signals from K+ efflux, ROS generation or lysosomal dysfunction activate the NLRP3 inflammasome. The activated caspase-1 potentiates the generation of active IL-1, IL-18 and gasdermin. The latter provokes pore formation in the cellular membrane, causing cell death and the release of inflammation mediators. On the right are reported the principal pathologic mechanisms in common liver diseases leading to NLRP3 activation: (1) HBV and HCV infection, (2) ARLD, (3) NASH and liver injury in sepsis and (4) the accumulation of lipid droplets.
Figure 2
Figure 2
A brief outline of the therapeutic effects of the NLRP3 system in HCC.
See this image and copyright information in PMC

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