NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer.

Margherita Sonnessa,Antonella Cioffi,Concetta Saponaro,Anita Mangia,Nicola Silvestris,Oronzo Brunetti,Francesco A Zito

doi:10.3389/fonc.2020.01587

Abstract

The tumor microenvironment (TME) is crucial in cancer onset, progression and response to treatment. It is characterized by an intricate interaction of immune cells and cytokines involved in tumor development. Among these, inflammasomes are oligomeric molecular platforms and play a key role in inflammatory response and immunity. Inflammasome activation is initiated upon triggering of pattern recognition receptors (Toll-like receptors, NOD-like receptors, and Absent in melanoma like receptors), on the surface of immune cells with the recruitment of caspase-1 by an adaptor apoptosis-associated speck-like protein. This structure leads to the activation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and participates in different biological processes exerting its effects. To date, the Nod–Like Receptor Protein 3 (NLRP3) inflammasome has been well studied and its involvement has been established in different cancer diseases. In this review, we discuss the structure, biology and mechanisms of inflammasomes with a special focus on the specific role of NLRP3 in breast cancer (BC) and in the sub-group of triple negative BC. The NLRP3 inflammasome and its down-stream pathways could be considered novel potential tumor biomarkers and could open new frontiers in BC treatment.

Highlights

Cancer is a multifactorial disease in which the tumor microenvironment (TME) plays a central role through the release of inflammatory cytokines, chemokines and growth factors, which are major components in inflammation and cancer [1, 2]
Nod–Like Receptor Protein 3 (NLRP3) inflammasome activation and IL-1β secretion play a critical role in promoting tumor growth and metastasis in breast cancer (BC) [43] and they are associated with tumor proliferation, angiogenesis, invasiveness, relapse and progression [69,70,71,72] (Figure 3)
This study demonstrated that silibinin impaired mitochondrial activity and reactive oxygen species (ROS) generation, leading to inhibition of both the NLRP3 inflammasome pathway and CASP-1/IL-1β expression, reducing cell migration and invasion [101]

Summary

Introduction

Cancer is a multifactorial disease in which the tumor microenvironment (TME) plays a central role through the release of inflammatory cytokines, chemokines and growth factors, which are major components in inflammation and cancer [1, 2]. The balance of TME molecules, pro and anti-angiogenic factors (VEGF, HIF-1α, and IL-12), and immune cells (cancer-associated fibroblasts, tumor-infiltrating immune cells, and TAMs) and the expression of receptors of the innate immune system (TLRs, NLRs) can influence the function of inflammasomes [36, 43, 44]. These studies have demonstrated that inflammasomes support tumorigenesis and cell proliferation in lung cancer by releasing inflammatory cytokines and decreasing immune function.

Results

Conclusion