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

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

doi:10.1126/scitranslmed.aal1571

Research ArticleCancer

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

View ORCID ProfileGiovanna Cutrona¹,*,†,
View ORCID ProfileClaudio Tripodo²,*,
Serena Matis¹,
Anna Grazia Recchia³,⁴,
Carlotta Massucco¹,
Marina Fabbi⁵,
Monica Colombo¹,
Laura Emionite⁶,
Sabina Sangaletti⁷,
View ORCID ProfileAlessandro Gulino²,
Daniele Reverberi¹,
Rosanna Massara¹,
Simona Boccardo⁸,
Daniela de Totero¹,
Sandra Salvi⁸,
Michele Cilli⁶,
View ORCID ProfileMariavaleria Pellicanò³,⁴,
View ORCID ProfileMartina Manzoni⁹,¹⁰,
Sonia Fabris¹⁰,
Irma Airoldi¹¹,
Francesca Valdora¹,¹²,
View ORCID ProfileSilvano Ferrini⁵,
Massimo Gentile³,⁴,
Ernesto Vigna³,⁴,
Sabrina Bossio⁴,
Laura De Stefano⁴,
Angela Palummo⁴,
Giovanni Iaquinta⁴,
Martina Cardillo¹²,
Simonetta Zupo¹³,
Giannamaria Cerruti¹³,
Adalberto Ibatici¹⁴,
View ORCID ProfileAntonino Neri⁹,¹⁰,
View ORCID ProfileFranco Fais¹,¹²,
Manlio Ferrarini¹⁵ and
Fortunato Morabito³,⁴

¹Molecular 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.
²Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo School of Medicine, 90127 Palermo, Italy.
³Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.
⁴Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.
⁵Biotherapy Unit, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.
⁶Animal Facility, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.
⁷Molecular Immunology Unit, IRCCS Istituto Nazionale Tumori, 20134 Milan, Italy.
⁸Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.
⁹Department of Oncology and Hemato-Oncology, University of Milano, 20122 Milan, Italy.
¹⁰Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
¹¹Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
¹²Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
¹³Molecular Diagnostic Unit, Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.
¹⁴Hematology and Bone Marrow Transplantation Unit, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.
¹⁵Scientific Direction, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

↵†Corresponding author. Email: giovanna.cutrona{at}hsanmartino.it

↵* These authors contributed equally to this work.

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Science Translational Medicine 14 Feb 2018:
Vol. 10, Issue 428, eaal1571
DOI: 10.1126/scitranslmed.aal1571

Giovanna Cutrona

1Molecular 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.

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ORCID record for Giovanna Cutrona
For correspondence: giovanna.cutrona@hsanmartino.it

Claudio Tripodo

2Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo School of Medicine, 90127 Palermo, Italy.

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Serena Matis

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Anna Grazia Recchia

3Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Carlotta Massucco

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Marina Fabbi

5Biotherapy Unit, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Monica Colombo

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Laura Emionite

6Animal Facility, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Sabina Sangaletti

7Molecular Immunology Unit, IRCCS Istituto Nazionale Tumori, 20134 Milan, Italy.

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Alessandro Gulino

2Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo School of Medicine, 90127 Palermo, Italy.

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Daniele Reverberi

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Rosanna Massara

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Simona Boccardo

8Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Daniela de Totero

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Sandra Salvi

8Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Michele Cilli

6Animal Facility, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Mariavaleria Pellicanò

3Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Martina Manzoni

9Department of Oncology and Hemato-Oncology, University of Milano, 20122 Milan, Italy.

10Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

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Sonia Fabris

10Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

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Irma Airoldi

11Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.

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Francesca Valdora

12Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

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Silvano Ferrini

5Biotherapy Unit, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Massimo Gentile

3Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Ernesto Vigna

3Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Sabrina Bossio

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Laura De Stefano

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Angela Palummo

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Giovanni Iaquinta

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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Martina Cardillo

12Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

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Simonetta Zupo

13Molecular Diagnostic Unit, Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Giannamaria Cerruti

13Molecular Diagnostic Unit, Division of Histopathology and Cytopathology, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Adalberto Ibatici

14Hematology and Bone Marrow Transplantation Unit, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Antonino Neri

9Department of Oncology and Hemato-Oncology, University of Milano, 20122 Milan, Italy.

10Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

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Franco Fais

12Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

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Manlio Ferrarini

15Scientific Direction, IRCCS AOU San Martino–IST, 16132 Genoa, Italy.

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Fortunato Morabito

3Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

4Biotechnology Research Unit, Aprigliano, AO/Azienda Sanitaria Provinciale (ASP) of Cosenza, 87051 Cosenza, Italy.

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

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