(EN) Turning immunologically “cold” tumors “hot” is required for effective immune checkpoint inhibitor (ICI) treatment in hepatocellular carcinoma (HCC). Prof. Zhou Jingying’s team identified Fas-associated death domain (FADD) as a key molecule upregulated in HCC with dense tumor-infiltrating CD8+ T cells and better response to ICIs. Mechanistically, ICI treatment triggers FADD phosphorylation, nuclear translocation and interaction with Sam68, leading to NF-κB-mediated transcription of CCL5 and subsequent recruitment of CD8⁺ T cells, specifically in ICI-sensitive, but not ICI-resistant, tumors. Importantly, activating FADD through genetic or pharmacologic approaches overcame ICI resistance in orthotopic and spontaneous HCC mouse models in vivo. Together, these findings provide insights into combinatory immunotherapy approaches for HCC patients.

The research has been published in Cancer Research in July 2025.
Link:https://aacrjournals.org/cancerres/article/doi/10.1158/0008-5472.CAN-24-3854/763563/FADD-Activation-in-Hepatocellular-Carcinoma