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Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence.
Cutrona, Giovanna; Tripodo, Claudio; Matis, Serena; Recchia, Anna Grazia; Massucco, Carlotta; Fabbi, Marina; Colombo, Monica; Emionite, Laura; Sangaletti, Sabina; Gulino, Alessandro; Reverberi, Daniele; Massara, Rosanna; Boccardo, Simona; de Totero, Daniela; Salvi, Sandra; Cilli, Michele; Pellicanò, Mariavaleria; Manzoni, Martina; Fabris, Sonia; Airoldi, Irma; Valdora, Francesca; Ferrini, Silvano; Gentile, Massimo; Vigna, Ernesto; Bossio, Sabrina; De Stefano, Laura; Palummo, Angela; Iaquinta, Giovanni; Cardillo, Martina; Zupo, Simonetta; Cerruti, Giannamaria; Ibatici, Adalberto; Neri, Antonino; Fais, Franco; Ferrarini, Manlio; Morabito, Fortunato.
Afiliación
  • Cutrona G; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy. giovanna.cutrona@hsanmartino.it.
  • Tripodo C; Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo School of Medicine, 90127 Palermo, Italy.
  • Matis S; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Recchia AG; Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.
  • Massucco C; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Fabbi M; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Colombo M; Biotherapy Unit, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Emionite L; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Sangaletti S; Animal Facility, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Gulino A; Molecular Immunology Unit, IRCCS Istituto Nazionale Tumori, 20134 Milan, Italy.
  • Reverberi D; Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo School of Medicine, 90127 Palermo, Italy.
  • Massara R; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Boccardo S; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • de Totero D; Division of Histopathology and Cytopathology, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Salvi S; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Cilli M; Division of Histopathology and Cytopathology, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Pellicanò M; Animal Facility, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Manzoni M; Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.
  • Fabris S; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Airoldi I; Department of Oncology and Hemato-Oncology, University of Milano, 20122 Milan, Italy.
  • Valdora F; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Ferrini S; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Gentile M; Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
  • Vigna E; Molecular Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genoa, Italy.
  • Bossio S; Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
  • De Stefano L; Biotherapy Unit, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
  • Palummo A; Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.
  • Iaquinta G; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Cardillo M; Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.
  • Zupo S; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Cerruti G; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Ibatici A; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Neri A; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Fais F; Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
  • Ferrarini M; Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
  • Morabito F; Molecular Diagnostic Unit, Division of Histopathology and Cytopathology, IRCCS AOU San Martino-IST, 16132 Genoa, Italy.
Sci Transl Med ; 10(428)2018 02 14.
Article en En | MEDLINE | ID: mdl-29444977
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-12Rß1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rß1 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Transducción de Señal / Receptores de Interleucina / Interleucina-23 / Microambiente Tumoral Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Transducción de Señal / Receptores de Interleucina / Interleucina-23 / Microambiente Tumoral Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos