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Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development.

Cancer Cell 30, 308-323 (2016)
Publishers Version Postprint Research data DOI
Open Access Green
as soon as is submitted to ZB.
Hepatocellular carcinoma (HCC) represents a classic example of inflammation-linked cancer. To characterize the role of the immune system in hepatic injury and tumor development, we comparatively studied the extent of liver disease and hepatocarcinogenesis in immunocompromised versus immunocompetent Fah-deficient mice. Strikingly, chronic liver injury and tumor development were markedly suppressed in alymphoid Fah(-/-) mice despite an overall increased mortality. Mechanistically, we show that CD8(+) T cells and lymphotoxin β are central mediators of HCC formation. Antibody-mediated depletion of CD8(+) T cells as well as pharmacological inhibition of the lymphotoxin-β receptor markedly delays tumor development in mice with chronic liver injury. Thus, our study unveils distinct functions of the immune system, which are required for liver regeneration, survival, and hepatocarcinogenesis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hereditary Tyrosinemia Type-1; Hepatic-dysfunction; Tumor-development; T-cells; Hepatocytes; Cancer; Regeneration; Mice; Fumarylacetoacetate; Pathogenesis
Reviewing status