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

Claudio Tripodo, Alessandro Gulino, Daniele Reverberi, Rosanna Massara, Mariavaleria Pellicanò, Simona Boccardo, Francesca Valdora, Sabrina Bossio, Carlotta Massucco, Angela Palummo, Laura De Stefano, Laura Emionite, Anna Grazia Recchia, Martina Manzoni, Martina Cardillo, Antonino Neri, Giovanni Iaquinta, Sabina Sangaletti, Adalberto Ibatici, Irma AiroldiFranco Fais, Daniela De Totero, Sonia Fabris, Ernesto Vigna, Michele Cilli, Giannamaria Cerruti, Simonetta Zupo, Giovanna Cutrona, Manlio Ferrarini, Sandra Salvi, Marina Fabbi, Silvano Ferrini, Massimo Gentile, Fortunato Morabito, Monica Colombo, Serena Matis, Antonino Neri, Mariavaleria Pellicano'

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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-12Rb1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rb1 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.
Lingua originaleEnglish
pagine (da-a)eaal1571-
Numero di pagine0
RivistaScience Translational Medicine
Volume10
Stato di pubblicazionePublished - 2018

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Tripodo, C., Gulino, A., Reverberi, D., Massara, R., Pellicanò, M., Boccardo, S., Valdora, F., Bossio, S., Massucco, C., Palummo, A., De Stefano, L., Emionite, L., Recchia, A. G., Manzoni, M., Cardillo, M., Neri, A., Iaquinta, G., Sangaletti, S., Ibatici, A., ... Pellicano', M. (2018). Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence. Science Translational Medicine, 10, eaal1571-.