The multifaceted roles of inflammasome proteins in cancer

Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination.

Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported. Moreover, several studies report major inflammasome-independent functions for some of these innate receptor proteins such as absent in melanoma 2, nod-like receptor family pyrin containing 3 (NLRP3) or nod-like receptor family CARD containing 4 (NLRC4), functions exerted in epithelial cells as well as in immune cells.

The current review summarizes recent findings on the implication of inflammasomes and of absent in melanoma 2, NLRC4 and NLRP3 inflammasome-independent functions in cancer development and dissemination. Although contradictory in certain aspects, these studies highlight a lack of understanding of their mechanistic functions and regulations in cancer and the need for further investigations.