NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

Paolo Carrega, Fabrizio Loiacono, Emma Di Carlo, Angelo Scaramuccia, Marco Mora, Romana Conte, Roberto Benelli, Grazia Maria Spaggiari, Claudia Cantoni, Stefania Campana, Irene Bonaccorsi, Barbara Morandi, Mauro Truini, Maria Cristina Mingari, Lorenzo Moretta and Guido Ferlazzo ()
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Paolo Carrega: Istituto G. Gaslini
Fabrizio Loiacono: Istituto G. Gaslini
Emma Di Carlo: ‘G. d'Annunzio’ University
Angelo Scaramuccia: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Marco Mora: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Romana Conte: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Roberto Benelli: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Grazia Maria Spaggiari: University of Genova
Claudia Cantoni: Istituto G. Gaslini
Stefania Campana: Laboratory of Immunology and Biotherapy, University of Messina
Irene Bonaccorsi: Laboratory of Immunology and Biotherapy, University of Messina
Barbara Morandi: University of Genova
Mauro Truini: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Maria Cristina Mingari: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino/IST-Istituto Nazionale per la Ricerca sul Cancro
Lorenzo Moretta: IRCCS Bambino Gesù Children's Hospital
Guido Ferlazzo: Laboratory of Immunology and Biotherapy, University of Messina

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9280

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