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dc.contributor.authorTallerico, Rossana
dc.contributor.authorTodaro, Matilde
dc.contributor.authorDi Franco, Simone
dc.contributor.authorMacCalli, Cristina
dc.contributor.authorGarofalo, Cinzia
dc.contributor.authorSottile, Rosa
dc.contributor.authorPalmieri, Camillo
dc.contributor.authorTirinato, Luca
dc.contributor.authorPangigadde, Pradeepa N.
dc.contributor.authorLa Rocca, Rosanna
dc.contributor.authorMandelboim, Ofer
dc.contributor.authorStassi, Giorgio
dc.contributor.authorDi Fabrizio, Enzo M.
dc.contributor.authorParmiani, Giorgio
dc.contributor.authorMoretta, Alessandro
dc.contributor.authorDieli, Francesco
dc.contributor.authorKãrre, Klas
dc.contributor.authorCarbone, Ennio
dc.date.accessioned2015-08-03T10:58:32Z
dc.date.available2015-08-03T10:58:32Z
dc.date.issued2013-01-23
dc.identifier.citationTallerico, R., Todaro, M., Di Franco, S., Maccalli, C., Garofalo, C., Sottile, R., … Carbone, E. (2013). Human NK Cells Selective Targeting of Colon Cancer–Initiating Cells: A Role for Natural Cytotoxicity Receptors and MHC Class I Molecules. The Journal of Immunology, 190(5), 2381–2390. doi:10.4049/jimmunol.1201542
dc.identifier.issn00221767
dc.identifier.pmid23345327
dc.identifier.doi10.4049/jimmunol.1201542
dc.identifier.urihttp://hdl.handle.net/10754/562617
dc.description.abstractTumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.
dc.description.sponsorshipThis work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro, as well as by Axel Wenner-Gren Foundation Grant AIRC 10189 (to E. C.) and by Grants AIRC IG 8730 (to G. S.) and AIRC IG 10254 (to M. T.). R. S. is a recipient of a fellowship awarded by the Programma Operativo Regionale Calabria Fondo Sociale Europeo (2007-2013). S. D. F. is a Ph.D. student in the International Ph.D. Program in Immunopharmacology at the University of Palermo. R. T. is a Ph.D. student in the International Ph.D. Program in Molecular Oncology, Experimental Immunology and Development of Innovative Therapies.
dc.publisherThe American Association of Immunologists
dc.titleHuman NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentMaterial Science and Engineering Program
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalJournal of Immunology
dc.contributor.institutionDepartment of Experimental and Clinical Medicine, University of Magna Graecia Catanzaro, Viale Europa, Germaneto, 88100 Catanzaro, Italy
dc.contributor.institutionDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden
dc.contributor.institutionDepartment of Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italy
dc.contributor.institutionUnit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Molecular Oncology, San Raffaele Foundation Scientific Institute, 20132 Milan, Italy
dc.contributor.institutionNanostructures Department, Italian Institute of Technology, 16163 Genova, Italy
dc.contributor.institutionLautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel
dc.contributor.institutionDepartment of Experimental Medicine, University of Genova, 16148 Genova, Italy
dc.contributor.institutionDepartment of Biopathology, University of Palermo, 90134 Palermo, Italy
kaust.personDi Fabrizio, Enzo M.
dc.date.published-online2013-01-23
dc.date.published-print2013-03-01


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