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ZEB1 shapes AML immunological niches, suppressing CD8 T cell activity while fostering Th17 cell expansion.
Bassani, Barbara; Simonetti, Giorgia; Cancila, Valeria; Fiorino, Antonio; Ciciarello, Marilena; Piva, Annamaria; Khorasani, Arman Mandegar; Chiodoni, Claudia; Lecis, Daniele; Gulino, Alessandro; Fonzi, Eugenio; Botti, Laura; Portararo, Paola; Costanza, Massimo; Brambilla, Marta; Colombo, Giorgia; Schwaller, Juerg; Tzankov, Alexandar; Ponzoni, Maurilio; Ciceri, Fabio; Bolli, Niccolò; Curti, Antonio; Tripodo, Claudio; Colombo, Mario P; Sangaletti, Sabina.
Afiliação
  • Bassani B; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Simonetti G; Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
  • Cancila V; Tumor Immunology Unit, Department of Health Sciences, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy.
  • Fiorino A; Predictive Medicine: Molecular Bases of Genetic Risk Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Ciciarello M; CNR Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza," Unit of Bologna, Bologna, Italy; IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
  • Piva A; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Khorasani AM; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Chiodoni C; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Lecis D; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Gulino A; CGT Lab, Cogentech Società Benefit, Catania, Italy.
  • Fonzi E; Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola, Forlì-Cesena, Italy.
  • Botti L; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Portararo P; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
  • Costanza M; Neuro-Oncology Unit, Department of Clinical Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
  • Brambilla M; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Colombo G; Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara, Italy.
  • Schwaller J; University Children's Hospital Basel & Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Tzankov A; Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Ponzoni M; IRCCS Ospedale S. Raffaele, University Vita-Salute San Raffaele, Milan, Italy.
  • Ciceri F; IRCCS Ospedale S. Raffaele, University Vita-Salute San Raffaele, Milan, Italy.
  • Bolli N; Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy.
  • Curti A; Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Institute of Hematology "Seràgnoli," Bologna, Italy.
  • Tripodo C; Tumor Immunology Unit, Department of Health Sciences, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy; IFOM-ETS-The AIRC Institute of Molecular Oncology, Milan, Italy.
  • Colombo MP; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: mariopaolo.colombo@istitutotumori.mi.it.
  • Sangaletti S; Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: sabina.sangaletti@istitutotumori.mi.it.
Cell Rep ; 43(2): 113794, 2024 Feb 27.
Article em En | MEDLINE | ID: mdl-38363677
ABSTRACT
Acute myeloid leukemia (AML) progression is influenced by immune suppression induced by leukemia cells. ZEB1, a critical transcription factor in epithelial-to-mesenchymal transition, demonstrates immune regulatory functions in AML. Silencing ZEB1 in leukemic cells reduces engraftment and extramedullary disease in immune-competent mice, activating CD8 T lymphocytes and limiting Th17 cell expansion. ZEB1 in AML cells directly promotes Th17 cell development that, in turn, creates a self-sustaining loop and a pro-invasive phenotype, favoring transforming growth factor ß (TGF-ß), interleukin-23 (IL-23), and SOCS2 gene transcription. In bone marrow biopsies from AML patients, immunohistochemistry shows a direct correlation between ZEB1 and Th17. Also, the analysis of ZEB1 expression in larger datasets identifies two distinct AML groups, ZEB1high and ZEB1low, each with specific immunological and molecular traits. ZEB1high patients exhibit increased IL-17, SOCS2, and TGF-ß pathways and a negative association with overall survival. This unveils ZEB1's dual role in AML, entwining pro-tumoral and immune regulatory capacities in AML blasts.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Células Th17 Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Células Th17 Idioma: En Ano de publicação: 2024 Tipo de documento: Article