Extracellular Vesicles and the Inflammasome: An Intricate Network Sustaining Chemoresistance

Abstract

Extracellular vesicles (EVs) are membrane enclosed spherical particles devoted to intercellular communication. Cancer-derived EVs (Ca-EVs) are deeply involved in tumor microenvironment remodeling, modifying the inflammatory phenotype of cancerous and non-cancerous residing cells. Inflammation plays a pivotal role in initiation, development, and progression of many types of malignancies. The key feature of cancer-related inflammation is the production of cytokines that incessantly modify of the surrounding environment. Interleukin-1β (IL-1β) is one of the most powerful cytokines, influencing all the initiation-to-progression stages of many types of cancers and represents an emerging critical contributor to chemoresistance. IL-1β production strictly depends on the activation of inflammasome, a cytoplasmic molecular platform sensing exogenous and endogenous danger signals. It has been recently shown that Ca-EVs can activate the inflammasome cascade and IL-1β production in tumor microenvironment-residing cells. Since inflammasome dysregulation has been established as crucial regulator in inflammation-associated tumorigenesis and chemoresistance, it is conceivable that the use of inflammasome-inhibiting drugs may be employed as adjuvant chemotherapy to counteract chemoresistance. This review focuses on the role of cancer-derived EVs in tuning tumor microenvironment unveiling the intricate network between inflammasome and chemoresistance.

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…Physiologically, EVs are mediators of intercellular communication, while pathologically, they are involved in the initiation, exacerbation, and resistance in various diseases [ 280 ]. This leads to a large proportion of unsuccessful treatment regimens, specifically in cancer, due to the role of EVs in conferring resistance to cancer cells, via immune evasion and metastasis, as well as to chemotherapy [ 281 , 282 ].…”

EV-Mediated Chemoresistance in the Tumor Microenvironment: Is NF-κB a Player?

“…While these findings show how inflammasome affects EVs secretion, it is worthy to note that EVs can also influence inflammasome activity, thus revealing a bidirectional crosstalk. Hence, EVs can either positively or negatively affect inflammasome activity depending on the nature of the EVs releasing cells ( 148 ). Exosomes from LPS-treated macrophages are able to activate NLRP3 inflammasome in AML-12 hepatocytes ( 149 ).…”