title: A Tec kinase BTK inhibitor ibrutinib promotes maturation and activation of dendritic cells.
abstract: Ibrutinib, a BTK inhibitor, is currently used to treat various hematological malignancies. We evaluated whether ibrutinib treatment during development of murine bone marrow-derived dendritic cells (DCs) modulates their maturation and activation. Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs. Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation. LPS/ibrutinib-treated DCs displayed increased IFNβ and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone. Finally, LPS/ibrutinib-treated DCs promoted higher rates of CD4(+) T cell proliferation and cytokine production compared to LPS only stimulated DCs. Taken together, our results indicate that ibrutinib enhances the maturation and activation of DCs to promote CD4(+) T cell activation which could be exploited for the development of DC-based cancer therapies.
authors.affiliation: Department of Microbiology, The Ohio State University , Columbus, OH, USA.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Natarajan
authors.affiliation: Department of Environmental Health Sciences, College of Public Health, The Ohio State University , Columbus, OH, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Oghumu
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , Columbus, OH, USA.
authors.forename: Cesar
authors.initials: C
authors.lastname: Terrazas
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , Columbus, OH, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Varikuti
authors.affiliation: Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH, USA; Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, OH, USA; Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
keywords: BTK; Ibrutinib; LPS; T cell; dendritic cell