Ibrutinib is increasingly adopted for treating lymphoid malignancies. While growing amounts of data pile up about Ibrutinib mechanism of action on neoplastic B cells, little is known about its impact on other immune cells. Here we investigated the effect of Ibrutinib on monocyte/macrophage functions. (1) Ibrutinib treatment of purified human monocytes affected both chemoattractant-triggered inside-out as well as integrin-mediated outside-in signaling events, thus provoking defective adhesion and spreading on purified integrin ligands, respectively. (2) In in vitro cell-culture experiments, Ibrutinib promoted a differentiation shift of monocytes to fibrocyte-like cells, characterized by the acquisition of a typical elongated cell morphology. Importantly, this clear-cut shape transition also occurred upon culturing monocytes with sera derived from Ibrutinib-treated patients, thus clearly suggesting that the drug concentrations achievable in vivo can generate the phenotypic shift. (3) Ibrutinib-induced fibrocyte-like cells showed adhesion deficiency, altered phagocytic properties, and, with respect to macrophages, they acquired the capability of generating larger amounts of reactive oxygen species, possibly displaying different metabolic activities. Taken together, our results indicate that Ibrutinib has profound effects on the monocyte/macrophage immunobiology. They may finally shed some light about the biological ground of several Ibrutinib-related toxicities.
Pubmed ID: 30956776 RIS Download
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Database dedicated to the analysis of the genome of Escherichia coli. Its purpose is to collate and integrate various aspects of the genomic information from E. coli, the paradigm of Gram-negative bacteria. Colibri provides a complete dataset of DNA and protein sequences derived from the paradigm strain E. coli K-12, linked to the relevant annotations and functional assignments. It allows one to easily browse through these data and retrieve information, using various criteria (gene names, location, keywords, etc.). The data contained in Colibri originates from two major sources of information, the reference genomic DNA sequence from the E. coli Genome Project and the feature annotations from the EcoGene data collection.
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