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.File | Dimensione | Formato | |
---|---|---|---|
Iaquinta_Microenvironmental_2018.pdf
accesso aperto
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
1.17 MB
Formato
Adobe PDF
|
1.17 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.