Esparza-Baquer A, Labiano I, Sharif O, et al. -  Hepatocellular carcinoma (HCC) generally emerges on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. Mainly hepatic non-parenchymal cells express the triggering receptor expressed on myeloid cells 2 (TREM-2), which hinders Toll-like receptor signalling, safeguarding the liver from various hepatotoxic injuries. Researchers here examined how TREM-2 affects liver regeneration and hepatocarcinogenesis. Liver tissues of two independent cohorts of patients with HCC were analyzed for TREM-2 expression and were compared with control liver samples regarding TREM-2 expression. Further, they conducted experimental HCC and liver regeneration models in wild type and Trem-2^-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids.

Human HCC tissue, mouse models of liver regeneration and HCC showed upregulation of TREM-2 expression. In Trem-2^-/- mice, more liver tumors developed irrespective of size after diethylnitrosamine (DEN) administration and there were exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. These findings suggest the protective role of TREM-2 in hepatocarcinogenesis via different pleiotropic effects, emphasizing investigation for TREM-2 agonism as it might beneficially affect HCC pathogenesis in a multifactorial manner.