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, Guido Ferlazzo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number8280
JournalNature Communications
Publication statusPublished - Sept 23 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)


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