The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers

ABSTRACT

Introduction: Inflammasomes are large multimeric intracellular complexes that are capable of maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18, in response to danger signal molecules. As a member of the inflammasome family, the NLRP3 inflammasome has recently been under intense investigation revealing its possible role in several human diseases especially cancers.

Areas covered: In this review, we will discuss the biology and mechanism of NLRP3 inflammasome activation, its role in specific types of tumors and the novel therapeutic modalities targeting this complex.

Expert opinion: The NLRP3 inflammasome and its components including the adapter apoptosis-associated speck-like (ASC) protein and caspase-1 impose different and sometimes contrasting effects in tumorigenesis depending on various contexts. Considering the novel role of this complex in the initiation and progression of neoplasia, the NLRP3 inflammasome and its pathways provide desirable therapeutic targets for prevention, treatment, and prognosis of certain types of cancer. To date, several agents have been introduced for this purpose, some of which have shown promising results in the clinic.

KEYWORDS:

• NLRP3 inflammasome
• IL-1β/IL-18
• cancer
• immunotherapy

Article highlights

• Inflammasomes are a critical part of innate immunity, playing the role of signaling platforms for products associated with stress and damage.

• The NLRP3 inflammasome is the most recognized member of this family which reacts to a wide range of stimuli ranging from infectious agents to endogenous ligands.

• Dysregulation of the NLRP3 inflammasome plays a contrary role in inflammation-induced cancers.

• This double-edged sword function not only differs in various cancers but is also tissue-specific.

• To date, a diverse range of agents such as inflammasome activation inhibitors, antagonists and monoclonal antibodies have been introduced for cancer treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.