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

Nat Commun. 2015 Sep 23;6:8280. doi: 10.1038/ncomms9280.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Cell Line, Tumor
  • Chemokines / metabolism
  • Humans
  • Lung Neoplasms / immunology*
  • Lymphocytes / metabolism*
  • Receptors, Natural Cytotoxicity Triggering / metabolism*


  • Chemokines
  • Receptors, Natural Cytotoxicity Triggering