We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Microenvironment regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence.
- Authors
Cutrona, Giovanna; Tripodo, Claudio; Matis, Serena; Colombo, Monica; Fabbi, Marina; Ibatici, Adalberto; de Totero, Daniela; Morabito, Fortunato; Ferrarini, Manlio; Fais, Franco
- Abstract
The development and progression of Chronic Lymphocytic Leukemia (CLL) require co-operation of both microenvironment and cytokines. Investigating the IL-23R/IL-23 axis we found that circulating cells of early-stage CLL patients with shorter time-to-treatment (but not of those with a more benign course) expressed a defective form of the IL-23R complex lacking the IL-12Rß1 chain. However, the cells from both patient groups expressed the com-plete IL-23R complex in tissue infiltrates and could be induced to express it when co-cultured with activated T cells or other CD40L-bearing cells. IL-23 production by CLL cells activated in vitro in this fashion and in lymphoid tissues was observed suggesting the exist-ence of an autocrine/ paracrine loop causing CLL cell proliferation. Culture of CLL cells with stromal cells, nurse like cells and stimulation with anti IgM antibodies and IL-4 failed to activate this loop. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 anti-body proved effective in controlling disease onset/expansion in xenografted mice, suggesting potential therapeutic strategies.
- Subjects
DISEASE progression; CHRONIC lymphocytic leukemia diagnosis; CHRONIC lymphocytic leukemia treatment
- Publication
Italian Journal of Anatomy & Embryology / Archivio Italiano di Anatomia Ed Embriologia, 2017, Vol 122, p69
- ISSN
1122-6714
- Publication type
Abstract