Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from 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-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence / Giovanna, Cutrona; Claudio, Tripodo; Matis, S; Anna Grazia, Recchia; Massucco, C; Marina, Fabbi; Monica, Colombo; Emionite, L; Sabina, Sangaletti; Alessandro, Gulino; Reverberi, D; Massara, R; Boccardo, S; Daniela de, Totero; Salvi, S; Cilli, M; Mariavaleria, Pellicano; Martina, Manzoni; Sonia, Fabris; Irma, Airoldi; Valdora, F; Silvano, Ferrini; Massimo, Gentile; Vigna, E; Bossio, S; De Stefano, L; Palummo, A; Iaquinta, G; Martina, Cardillo; Simona, Zupo; Cerruti, G; Ibatici, A; Antonino, Neri; Franco, Fais; Ferrarini, M; Morabito, F. - In: SCIENCE TRANSLATIONAL MEDICINE. - ISSN 1946-6242. - 10:428(2018). [10.1126/scitranslmed.aal1571]

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

Massara R;Salvi S;De Stefano L;Iaquinta G;Cerruti G;
2018

Abstract

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from 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-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.
2018
CLL; lymphocytic leukemia indolence; IL-23R/IL-23
01 Pubblicazione su rivista::01a Articolo in rivista
Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence / Giovanna, Cutrona; Claudio, Tripodo; Matis, S; Anna Grazia, Recchia; Massucco, C; Marina, Fabbi; Monica, Colombo; Emionite, L; Sabina, Sangaletti; Alessandro, Gulino; Reverberi, D; Massara, R; Boccardo, S; Daniela de, Totero; Salvi, S; Cilli, M; Mariavaleria, Pellicano; Martina, Manzoni; Sonia, Fabris; Irma, Airoldi; Valdora, F; Silvano, Ferrini; Massimo, Gentile; Vigna, E; Bossio, S; De Stefano, L; Palummo, A; Iaquinta, G; Martina, Cardillo; Simona, Zupo; Cerruti, G; Ibatici, A; Antonino, Neri; Franco, Fais; Ferrarini, M; Morabito, F. - In: SCIENCE TRANSLATIONAL MEDICINE. - ISSN 1946-6242. - 10:428(2018). [10.1126/scitranslmed.aal1571]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1686398
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