摘要
Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide.HCC initiates as a consequence of chronic liver damage and inflammation caused by hepatitis B and C virus infections,excessive alcohol con sumption,or non-alcoholic fatty liver disease(NAFLD).Until recently,no effective treat-ments for advanced HCC were available and the 5-year survival rate had remained below 8%for many years.New insights into the mechanisms that drive the development of NAFLD-related HCC indicate that loss of T-cell-mediated immunosurveillance plays a cardinal role in tumor growth and malignant progression,in addition to previously identifhed inflammation-driven compensatory proliferation.Recently completed groundbreaking clinical studies have shown that treatments that restore antitumor immunity represent a highly effective therapeutic option for approximately 20%of advanced HCC patients.Understanding the causes of inflammation-driven immunosuppression and immune system dysfunction in the 80%of patients who fail to reignite antitumor immunity despite treatment with checkpoint inhibitors should lead to further and even more dramatic improvements in HCC immunotherapy.
基金
supported by the NIH/NCI(R01CA211794)
the NIEHS Superfund Research Program(P42ES010337)
the Tower Cancer Research Foundation(Senior Investigator Grant).