Innovations in exploring the immune ecosystem of liver cancer for precision medicine

Liver cancer continues to be a significant global health challenge, with limited treatment options and poor prognosis. The immune microenvironment has increasingly been identified as a crucial factor in disease progression and therapeutic response. To better understand the complex interactions between tumor genetics and the immune microenvironment, we employed somatic genome-editing in mouse models to mimic the genetic landscapes observed in human liver cancers, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). These two types of liver cancer are characterized by distinct driver gene mutations. Our mouse models can simulate the multifaceted etiological aspects, including steatosis, offering a more accurate representation of clinical scenarios. As a result, these models are effective tools for investigating disease pathology and evaluating potential therapeutic interventions. Here, we will illustrate how we have integrated these mouse models with advanced immunophenotyping technologies to thoroughly map the mechanisms that influence the tumor microenvironment. We have shown that these models can be used to predict responses to immunotherapy and post-surgical resection. They are valuable for understanding the underlying mechanisms of driver gene mutations in drug resistance and the immune ecosystem of tumors. Such insights are critical for designing personalized therapeutics to treat patients with diverse genetic profiles and etiologies, thereby advancing personalized medicine for liver cancer.