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

SIMPLE SUMMARY: The Hepatocellular Carcinoma (HCC) remains a major concern for the public health. The pandemic of metabolic syndrome in the Western societies and the considerable amounts of viral hepatitis in the underdeveloped countries keep fueling s the development of HCC. The hepatotropic viruses evade the NLRP3 inflammasome in order to sustain the chronicity of infection leading to cirrhosis while in the established tumors the activation of NLRP3 promotes several pro-tumorigenic effects. That leads to substantial economic burden for the societies and alternative therapeutic targets should be investigated. Reviewing past and more recent literature it can be deduced that the NLRP3 inflammasome could be an ideal therapeutic effects and it should be studied in more depth. 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.