Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

Handle URI:
http://hdl.handle.net/10754/562617
Title:
Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules
Authors:
Tallerico, Rossana; Todaro, Matilde; Di Franco, Simone; MacCalli, Cristina; Garofalo, Cinzia; Sottile, Rosa; Palmieri, Camillo; Tirinato, Luca; Pangigadde, Pradeepa N.; La Rocca, Rosanna; Mandelboim, Ofer; Stassi, Giorgio; Di Fabrizio, Enzo M. ( 0000-0001-5886-4678 ) ; Parmiani, Giorgio; Moretta, Alessandro; Dieli, Francesco; Kãrre, Klas; Carbone, Ennio
Abstract:
Tumor 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.
KAUST Department:
Physical Sciences and Engineering (PSE) Division; Biological and Environmental Sciences and Engineering (BESE) Division; Materials Science and Engineering Program
Publisher:
American Association of Immunologists
Journal:
Journal of Immunology
Issue Date:
23-Jan-2013
DOI:
10.4049/jimmunol.1201542
PubMed ID:
23345327
Type:
Article
ISSN:
00221767
Sponsors:
This 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.
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Materials Science and Engineering Program; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorTallerico, Rossanaen
dc.contributor.authorTodaro, Matildeen
dc.contributor.authorDi Franco, Simoneen
dc.contributor.authorMacCalli, Cristinaen
dc.contributor.authorGarofalo, Cinziaen
dc.contributor.authorSottile, Rosaen
dc.contributor.authorPalmieri, Camilloen
dc.contributor.authorTirinato, Lucaen
dc.contributor.authorPangigadde, Pradeepa N.en
dc.contributor.authorLa Rocca, Rosannaen
dc.contributor.authorMandelboim, Oferen
dc.contributor.authorStassi, Giorgioen
dc.contributor.authorDi Fabrizio, Enzo M.en
dc.contributor.authorParmiani, Giorgioen
dc.contributor.authorMoretta, Alessandroen
dc.contributor.authorDieli, Francescoen
dc.contributor.authorKãrre, Klasen
dc.contributor.authorCarbone, Ennioen
dc.date.accessioned2015-08-03T10:58:32Zen
dc.date.available2015-08-03T10:58:32Zen
dc.date.issued2013-01-23en
dc.identifier.issn00221767en
dc.identifier.pmid23345327en
dc.identifier.doi10.4049/jimmunol.1201542en
dc.identifier.urihttp://hdl.handle.net/10754/562617en
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.en
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.en
dc.publisherAmerican Association of Immunologistsen
dc.titleHuman NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i moleculesen
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentMaterials Science and Engineering Programen
dc.identifier.journalJournal of Immunologyen
dc.contributor.institutionDepartment of Experimental and Clinical Medicine, University of Magna Graecia Catanzaro, Viale Europa, Germaneto, 88100 Catanzaro, Italyen
dc.contributor.institutionDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Swedenen
dc.contributor.institutionDepartment of Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italyen
dc.contributor.institutionUnit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Molecular Oncology, San Raffaele Foundation Scientific Institute, 20132 Milan, Italyen
dc.contributor.institutionNanostructures Department, Italian Institute of Technology, 16163 Genova, Italyen
dc.contributor.institutionLautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, 91120 Jerusalem, Israelen
dc.contributor.institutionDepartment of Experimental Medicine, University of Genova, 16148 Genova, Italyen
dc.contributor.institutionDepartment of Biopathology, University of Palermo, 90134 Palermo, Italyen
kaust.authorDi Fabrizio, Enzo M.en

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