Supporting data for Tumor intrinsic pathways dictate the immune landscape and responses to immune checkpoint inhibitors in liver cancer
Immune checkpoint inhibitors (ICIs) have reached unprecedented clinical success in multiple cancer types including hepatocellular carcinoma (HCC). However, there is still a signficant proportion of HCC patients not responding to ICIs. My studies revealed that tumor-intrinsic oncogenic pathways could determine the intratumoral immune composition and thus the response to ICIs. By studying anti-PD-1-resistant mouse HCC model, I identified another immune checkpoint, TIGIT, being upregulated after anti-PD-1 treatment. TIGIT upregulation conferred anti-PD-1 resistance. Co-blockade of PD-1 and TIGIT could overcome this resistance.
Quantitaive real-time polymerase chain reaction (qRT-PCR) was used to examine key HCC genes expressed in mouse HCC tumors, proinflammatory chemokines upregulated in immune-inflamed tumors, and PVR family gene expression (ligands of TIGIT) in HCC cell lines.