Non-alcoholic Fatty Liver Disease Affect Efficacy of Immune Checkpoint Inhibitors for Patients with Hepatocellular Carcinoma: Manifestations and Mechanisms
10.3971/j.issn.1000-8578.2022.22.0562
- VernacularTitle:非酒精性脂肪肝对免疫检查点抑制剂治疗肝细胞癌疗效的影响及机制研究进展
- Author:
Ye YUAN
1
;
Hui PENG
;
De'an TIAN
Author Information
1. Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Publication Type:Research Article
- Keywords:
Non-alcoholic fatty liver disease;
Hepatocellular carcinoma;
Immune checkpoint blockade;
Efficacy
- From:
Cancer Research on Prevention and Treatment
2022;49(11):1195-1201
- CountryChina
- Language:Chinese
-
Abstract:
The number of patients with the combination of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) is gradually increasing. In recent years, the immunotherapy has become a new effective way to treat unresectable HCC. The clinical research revealed that the NAFLD could affect the efficacy of immunotherapy treating the HCC. But the mechanism is complicated. The major routes are CD8+PD-1+T cells increasing in NAFLD cause the deficiency in cell proliferation ability; Zn64 activates the anti-tumor immune response of the CSF1; PCSK9 downregulates the LDLR level to suppress the immune response of the CD8+T cells in tumor microenvironment; loss of the immune response induces the liver damage. Researches had indicated that the combination of lenvatinib, PKCa inhibitor, PCSK9 protein inhibition, ferroptosis inducer, and HIF2a small molecule inhibitor can improve the efficacy of immune checkpoint inhibitors for NAFLD-associated hepatocellular carcinoma. This review focuses on the impact of NAFLD on tumor microenvironment and how the NAFLD affect the immune check-point inhibitor effect and to discover the exact mechanism.
