期刊
ONCOIMMUNOLOGY
卷 5, 期 6, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1151592
关键词
BTK; dendritic cell; Ibrutinib; LPS; T cell
资金
- National Institutes of Health [R03AI090231, RC4AI092624, R34AI100789, R21AT004160, R03CA164399, R01CA162411, R35CA197734]
- National Institute of Dental and Craniofacial Research Training Grant [T32DE014320]
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 CD8(+) and downregulated Ly6C expression by DCs. Additionally, ibrutinib treatment led to an increase in MHC-IIC, CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation. LPS/ibrutinib-treated DCs displayed increased IFN beta 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.
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