title: NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures.
abstract: Tertiary lymphoid structures (TLSs) are a common finding in non-small cell lung cancer (NSCLC) and are predictors of favourable clinical outcome. Here we show that NCR(+) innate lymphoid cell (ILC)-3 are present in the lymphoid infiltrate of human NSCLC and are mainly localized at the edge of tumour-associated TLSs. This intra-tumoral lymphocyte subset is endowed with lymphoid tissue-inducing properties and, on activation, produces IL-22, TNF-α, IL-8 and IL-2, and activates endothelial cells. Tumour NCR(+)ILC3 may interact with both lung tumour cells and tumour-associated fibroblasts, resulting in the release of cytokines primarily on engagement of the NKp44-activating receptor. In patients, NCR(+)ILC3 are present in significantly higher amounts in stage I/II NSCLC than in more advanced tumour stages and their presence correlate with the density of intratumoral TLSs. Our results indicate that NCR(+)ILC3 accumulate in human NSCLC tissue and might contribute to the formation of protective tumour-associated TLSs.
authors.affiliation: Istituto G. Gaslini, Genova 16148, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carrega
authors.affiliation: Istituto G. Gaslini, Genova 16148, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loiacono
authors.affiliation: Department of Medicine and Sciences of Aging, 'G. d'Annunzio' University, Chieti 66013, Italy.|Centro di Scienze dell'Invecchiamento, Fondazione Università 'G. d'Annunzio', Chieti 66013, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Scaramuccia
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mora
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Benelli
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genoa 16132, Italy.
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Spaggiari
authors.affiliation: Istituto G. Gaslini, Genova 16148, Italy.|Department of Experimental Medicine (DIMES), University of Genova, Genoa 16132, Italy.|Center of Excellence in Biomedical Research, Centro di Eccellenza per la Ricerca Biomedica (CEBR), University of Genova, Genoa 16132, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.affiliation: Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina 98125, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Campana
authors.affiliation: Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina 98125, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bonaccorsi
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genoa 16132, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Morandi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy.|Department of Experimental Medicine (DIMES), University of Genova, Genoa 16132, Italy.|Center of Excellence in Biomedical Research, Centro di Eccellenza per la Ricerca Biomedica (CEBR), University of Genova, Genoa 16132, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.affiliation: Department of Immunology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina 98125, Italy.|Cell Therapy Program, Azienda Ospedaliera Universitaria Policlinico 'Gaetano Martino', Messina 98125, Italy.
authors.forename: Guido
authors.identifier: http://orcid.org/0000-0002-3874-8554
authors.initials: G
authors.lastname: Ferlazzo
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008214:Lymphocytes / Q000378:metabolism*; D055636:Receptors, Natural Cytotoxicity Triggering / Q000378:metabolism*
chemical_list: D018925:Chemokines; D055636:Receptors, Natural Cytotoxicity Triggering