ArticleScientific reports2018
Idelalisib impairs TREM-1 mediated neutrophil inflammatory responses.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Bullous Pemphigoid Develops Independently of DAP12.Biomolecules · 2025Article
- Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in Inflammation and Disease: Mechanisms, Therapeutic Potential, and Future Directions.International journal of molecular sciences · 2025Review
- TREM-1 as a novel immunotherapeutic target to treat pancreatic ductal adenocarcinoma.Molecular therapy. Oncology · 2025Article
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- Transient inhibition of neutrophil functions enhances the antitumor effect of intravenously delivered oncolytic vaccinia virus.Cancer science · 2024Article
- Targeting the tumor microenvironment in chronic lymphocytic leukemia.Haematologica · 2021Review
- Precision cut lung slices: an ex vivo model for assessing the impact of immunomodulatory therapeutics on lung immune responses.Archives of toxicology · 2021Article
- Kinase inhibitors developed for treatment of hematologic malignancies: implications for immune modulation in COVID-19.Blood advances · 2021Review
- New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease.Frontiers in immunology · 2021Review
- Identification of Dendritic Cell Maturation, TLR, and TREM1 Signaling Pathways in theFrontiers in veterinary science · 2021Article
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: clinical and pathological features.Journal of neurovirology · 2020Article
- Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis.Immunobiology · 2020Article
- TREM-1 Is Upregulated in Experimental Periodontitis, and Its Blockade Inhibits IL-17A and RANKL Expression and Suppresses Bone loss.Journal of clinical medicine · 2019Article
- Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis.Blood · 2019Article
- Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triggering receptor expressed on myeloid cells (TREM)-1 on polymorphonuclear neutrophils (PMN) regulates innate immune activation in infectious and non-infectious conditions. TREM-1 ligation activates phosphatidyl-inositol 3 kinase (PI3K) triggering all neutrophil effector functions. As idelalisib is a PI3K inhibitor in clinical use for the treatment of non-Hodgkin lymphomas, we asked whether this inhibitor affects PMN functionalities. We analyzed PMNs from healthy donors or lymphoma patients for oxidative burst, phagocytosis, activation markers and IL-8 release upon TREM-1 or TLR ligation ex vivo. In addition, we performed western blot analyses to characterize the signaling events inhibited by idelalisib and other PI3K inhibitors. Upon TREM-1 ligation, the oxidative burst, degranulation, L-selectin shedding and cytokine release were all strongly reduced in the presence of idelalisib along impaired phosphorylation of P38, AKT and ERK by western blot analyses. In line with this, PMNs from patients receiving idelalisib also displayed an impaired TREM-1 mediated PMN activation ex vivo. In conclusion, PI3K inhibitors might cause a neutropenia-like susceptibility to infections in patients by leading to impaired PMN functionality. This should be considered when evaluating patients for infections treated with such inhibitors in daily clinical routine.
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