TLR4 and hepatocellular carcinoma: Paradoxically, targeted mutation of key regulators of inflammatory responses, such as the Tlr2 and Tlr4 genes, which reduces intrahepatic inflammatory responses, has been shown to dramatically promote DEN-induced HCC25,26, although several groups reported that germline deletion of either Tlr4 or Tlr2 decreased HCC development27,28.