title: The immunoreceptor NKG2D promotes tumour growth in a model of hepatocellular carcinoma.
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+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.
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Sheppard
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Joana
authors.initials: J
authors.lastname: Guedes
authors.affiliation: Department of Cellular Pathology, Imperial College London, W2 1NY London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Mroz
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Anastasia-Maria
authors.initials: AM
authors.lastname: Zavitsanou
authors.affiliation: Department of Cellular Pathology, Imperial College London, W2 1NY London, UK.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kudo
authors.affiliation: Facility for Imaging by Light Microscopy, Imperial College London, SW7 2AZ London, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rothery
authors.affiliation: Department of Mathematics, National Technical University of Athens, Zografou, 15773 Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Angelopoulos
authors.affiliation: Department of Cellular Pathology, Imperial College London, W2 1NY London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldin
authors.affiliation: Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Guerra
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D018450:Disease Progression; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000074322:Antineoplastic Agents, Immunological; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D025521:Tumor Suppressor Proteins; D004052:Diethylnitrosamine