Inflammasome Activation in Cancer Pathophysiology

Inflammasomes are cytosolic multi-protein assemblies that sense cellular stress or damage-associated molecular patterns and activate caspase-1, leading to maturation of interleukin-1β and interleukin-18 and execution of pyroptotic cell death. In the context of cancer, inflammasome activation shapes the tumour microenvironment by influencing cytokine secretion, immune-cell recruitment and stromal remodelling. Chronic or dysregulated inflammasome signalling can foster malignant transformation through sustained inflammation, angiogenesis and immunosuppression, whereas acute or targeted activation may trigger pyroptosis in cancer cells and reinforce antitumour immunity. Key sensor proteins such as NLRP3 and NLRC4 detect a variety of endogenous and exogenous triggers, while adaptor molecules like ASC and effector proteases coordinate both pro-inflammatory cytokine release and gasdermin-mediated membrane permeabilisation. By modulating cell-death pathways, immune evasion strategies and therapeutic resistance, inflammasomes represent a double-edged sword in oncogenesis. Ongoing efforts aim to dissect context-specific roles across tumour types, to exploit inflammasome components as biomarkers of disease progression and to refine interventions that either inhibit chronic pro-tumour inflammation or harness controlled pyroptosis for improved clinical outcomes.

Research from Nature Portfolio

Recent studies have revealed that cancer-associated fibroblasts within solid tumours sense tissue damage via pattern-recognition receptors, activating NLRP3 inflammasome pathways that drive interleukin-1β secretion and promote an immunosuppressive microenvironment. Ablation of NLRP3 or IL-1β in these stromal populations attenuates tumour growth and metastatic spread by reducing endothelial adhesion-molecule expression and myeloid-cell infiltration. Seminal work in breast cancer models has also demonstrated that pharmacological blockade of IL-1 receptor signalling diminishes inflammasome-mediated recruitment of myeloid-derived suppressor cells and tumour-associated macrophages, resulting in decreased primary tumour burden and metastatic foci. These findings underscore the potential of targeting inflammasome-driven cytokine networks to remodel the tumour niche and enhance the efficacy of immunotherapy.

Inflammasome Activation in Cancer Pathophysiology publication trend

The graph below shows the total number of articles in inflammasome activation in cancer pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Inflammasome: A cytosolic protein complex that assembles upon detection of danger signals, activating caspase-1 to process pro-inflammatory cytokines and initiate pyroptosis.

Pyroptosis: A form of lytic, pro-inflammatory cell death characterised by gasdermin-mediated pore formation, cytokine release and immune activation.

NLRP3: A sensor protein of the Nod-like receptor family that recognises a broad spectrum of stimuli and nucleates inflammasome assembly.

Gasdermin D: An effector protein cleaved by caspase-1; its N-terminal fragment forms pores in the plasma membrane to execute pyroptosis.

Damage-Associated Molecular Patterns (DAMPs): Endogenous molecules released upon cellular injury that trigger innate immune receptors and inflammasome activation.

References

1. Involvement of inflammasomes in tumor microenvironment and tumor therapies. Journal of Hematology & Oncology (2023).
2. Targeting inflammasome/IL-1 pathways for cancer immunotherapy. Scientific Reports (2016).
3. NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis. Nature Communications (2019).
4. Sorcin regulate pyroptosis by interacting with NLRP3 inflammasomes to facilitate the progression of hepatocellular carcinoma. Cell Death & Disease (2023).
5. Inflammasomes in cancer: a double-edged sword. Protein & Cell (2014).