Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase 1, thereby promoting the secretion of bioactive interleukin-1β (IL-1β) and IL-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signalling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis and metastasis. Conversely, inflammasome signalling also contributes to tumour suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the importance of environmental factors, such as diet and gut microbiota, in inflammasome signalling, which in turn influences tumorigenesis. In this Review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as therapeutic targets.

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Diverging inflammasome signals in tumorigenesis and potential targeting

Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications.

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Cell or Cell Membrane-Based Drug Delivery Systems

There is currently no effective treatment for glioma, the most common type of brain tumour. Recent technological advances have made it possible to gain a more detailed understanding of the molecular processes underlying tumour cell differentiation and the findings suggest new opportunities for therapeutic intervention. Gliomas are the most common type of primary brain tumour and are often fast growing with a poor prognosis for the patient. Their complex cellular composition, diffuse invasiveness and capacity to escape therapies has challenged researchers for decades and hampered progress towards an effective treatment. Recent molecular characterization of tumour cells combined with new insights into cellular diversification that occurs during development, and the modelling of these processes in transgenic animals have enabled a more detailed understanding of the events that underlie gliomagenesis. Combining this enhanced understanding of the relationship between neural stem cell biology and the cell lineage relationships of tumour cells with model systems offers new opportunities to develop specific and effective therapies.

The neurobiology of gliomas: from cell biology to the development of therapeutic approaches

Interleukin (IL)-18 is a cytokine isolated as an important modulator of immune responses and subsequently shown to be pleiotropic. IL-18 and its receptors are expressed in the central nervous system (CNS) where they participate in neuroinflammatory/neurodegenerative processes but also influence homeostasis and behavior. Work on IL-18 null mice, the localization of the IL-18 receptor complex in neurons and the neuronal expression of decoy isoforms of the receptor subunits are beginning to reveal the complexity and the significance of the IL-18 system in the CNS. This review summarizes current knowledge on the central role of IL-18 in health and disease.

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Interleukin 18 in the CNS

Stem cell-based therapies are emerging as a promising strategy to tackle cancer. Multiple stem cell types have been shown to exhibit inherent tropism towards tumours. Moreover, when engineered to express therapeutic agents, these pathotropic delivery vehicles can effectively target sites of malignancy. This perspective considers the current status of stem cell-based treatments for cancer and provides a rationale for translating the most promising preclinical studies into the clinic.

Stem cell-based therapies for cancer treatment: separating hope from hype

Adenoviral‐mediated interleukin‐18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats

Objective To investigate the effect of hyperthermia in vitro on tight junctions between the endothelial cells of the blood-brain barrier. Methods An in vitro blood-brain barrier model was established by coculture of ECV304 cells with astrocytes. Transendothelial resistance (TER) of in vitro blood-brain barrier was determined by Millicell-ERS system, and the morphological change of tight junctions examined by silver staining. The expression level of zonula occluden-1(ZO-1) was analyzed by semi-quantitative reverse transcriptase-PCR. Results The integrity of tight junctions was disrupted and the expression level of ZO-1 decreased after treatement with hyperthermia. Conclusions Tight junctions between the endothelial cells of the blood-brain barrier can be destroyed by hyperthermia, and decreased expression level of ZO-1 induced by hyperthermia is one of the most important molecular mechanisms.

[Effect of hyperthermia on tight junctions between endothelial cells of the blood-brain barrier model in vitro].

Objective To investigate the relationship between aquaporin-4 (AQP4) water channel expression in astrocytes and brain edema caused by glioma. Methods The changes of water transport in in vitro blood-brain barrier models were examined using high-performance liquid chromatography (HPLC), and the expression level of AQP4 was assayed by semiquantitative RT-PCR. Results The water transport of the in vitro blood-brain barrier model from the luminal side to basolateral side was increased after coculture with glioma cells, which induced significantly decreased expression level of AQP4 in the astrocytes. Conclusions Glioma cells can promote water transport in in vitro blood-brain barrier model from the luminal side to abluminal side, and the brain edema induced by the glioma cells may not necessarily be the result of hyperpermeability of the blood-brain barrier to macromolecules in the plasma. The decreased expression level of AQP4 induced by glioma cells may be a molecular mechanism for neoplastic brain edema in patients with glioma.

Yi-zhao Chen

Papers

Adenoviral‐mediated interleukin‐18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats

[Effect of hyperthermia on tight junctions between endothelial cells of the blood-brain barrier model in vitro].

[Relationship between aquaporin-4 expression in astrocytes and brain edema caused by glioma].