The immunoreceptor NKG2D promotes tumour growth in a model of hepatocellular carcinoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28128200.
- Also identified by DOI 10.1038/ncomms13930 and PMC identifier 5290164.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8<sup>+</sup>T cells to the liver and exacerbated pro-inflammatory milieu. In addition, we show that NKG2D contributes to liver damage and consequent hepatocyte proliferation known to favour tumorigenesis. Thus, the NKG2D/NKG2D-ligand pathway provides an additional mechanism linking chronic inflammation to tumour development in hepatocellular carcinoma. Our findings expose the need to selectively target the types of cancer that could benefit from NKG2D-based immunotherapy.
Medical subject headings
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Liver Neoplasms, Experimental
- NK Cell Lectin-Like Receptor Subfamily K
- Tumor Suppressor Proteins