Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model

Abstract

Neutralization of IL-22 production from colonic innate lymphoid cells reduces dysplasia in bacterial-induced colon cancer by reducing proliferation of epithelial cells via reduced activation of Stat3.

Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet−/−.Rag2−/−(TRUC) mice

“…IL-22 mRNA is strongly up-regulated in the inflamed TRUC colon, making it unlikely that T-bet deficiency promotes colitis development in TRUC mice via a lack of IL-22-secreting NKp46 + ILCs. Both protective and disease-promoting roles have been described for IL-22 in mouse IBD models (44)(45)(46)(47), and it is feasible that IL-22 contributes to the development of colitis and colorectal carcinoma (48) in the TRUC model.…”

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

“…Although other lymphocytes of the tumour microenvironment may produce a similar pattern of soluble factors, including LTa/b and TNF-a, which are critical for the possible LTi properties, NCR þ ILC3 may play an exclusive role in the tumour microenvironment: first, they might be directly activated by cancer cells via NKp44 and therefore represent an early innate source of relevant cytokines; then compared with intratumoral NK cells, which may also be directly activated by cancer cells 42,48 , NCR þ ILC3 apparently lack inhibitory receptors controlling their activities and can also provide a unique innate source of IL-2, a crucial growth factor for the clonal expansion of tumour-specific lymphocytes. On the other hand, the role of an innate source of IL-22 within tumour microenvironment remains to be identified and might even favour cancer cell growth 49 . Nevertheless, it is noteworthy that tumour NCR þ ILC3 consistently released lower amount of IL-22 if compared with tonsillar counterpart (Supplementary Fig.…”

“…It should be mentioned, however, that activation of NCR þ ILC3 within tumours might not always represent a favourable event: a negative effect in colorectal cancer has recently been proposed for IL-22, which would act on epithelial cells and induce Stat3 phosphorylation and cell proliferation 49 . In this regard, it might be argued that, as mentioned above, lung tumour NCR þ ILC3 produce lower levels of IL-22 as compared with tonsillar and, probably, colon-associated NCR þ ILC3.…”

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

“…Adult LTi cells, a group‐3 innate lymphoid cell subset, bear many of the features of Th17 cells, which suggests an ancestral link between these cell types 26, 27. Both cells express the transcriptional regulator retinoic acid receptor‐related orphan receptor γ ; are responsive to IL‐23 and aryl hydrocarbon receptor ligands; and can produce IL‐17, IL‐22 and granulocyte–macrophage colony‐stimulating factor 28, 29, 30. Like Th17 and fetal LTi cells, innate lymphoid cells have been linked with lymphoid organogenesis.…”