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

P Carrega, F Loiacono, E Di Carlo… - Nature …, 2015 - nature.com
P Carrega, F Loiacono, E Di Carlo, A Scaramuccia, M Mora, R Conte, R Benelli
Nature communications, 2015nature.com
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 …
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.
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