Invariant natural killer T lymphocytes promote the development of intestinal tumors

CD1d-restricted natural killer T (NKT) cells are potent immuoregulatory cells. Activation of invariant NKT (iNKT) cells suppresses tumor formation in murine models, and iNKT cells can naturally protect against spontaneous tumors and enhance immune responses to infections. Further, NKT cells promote murine inflammatory bowel disease. Intestinal tumors develop in an environment of constant microbial pressure and inflammatory signals that enhance tumor formation. This raised the question whether NKT cells would suppress, through their anti-tumor function, or promote, by their proinflammatory capacity, tumor formation in this tissue. APC^min/+ mice develop intestinal tumors/polyps due to a mutation in the adenomatous polyposis coli gene, mutated in human colorectal cancer. We show that absence of all NKT cells, or iNKT cells, in APC^min/+ mice decreased the number of intestinal polyps with 60%. This was associated with reduced FoxP3 expression and increased expression of TH1-associated genes such as IFN-γ and iNOS in polyps. This suggests that iNKT cells promote intestinal polyp formation by enhancing FoxP3 Treg cells and local immunosuppression of anti-tumor TH1-immunity.