Journal of Hepatocellular Carcinoma (Jun 2024)
GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications
Abstract
Yi-Ning Du,1 Jin-Wei Zhao2 1Department of Medical Sciences, Li Ka-shing School of Medicine, University of Hong Kong, Hong Kong, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, Second Hospital of Jilin University, Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Jin-Wei Zhao, Department of Hepatopancreatobiliary Surgery, Second Hospital of Jilin University, Jilin University, No. 218, Ziqiang Road, Changchun, 130000, Jilin Province, People’s Republic of China, Tel +8615844089385, Email [email protected]: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally and the sixth most common cancer worldwide. Evidence shows that growth differentiation factor 15 (GDF15) contributes to hepatocarcinogenesis through various mechanisms. This paper reviews the latest insights into the role of GDF15 in the development of HCC, its role in the immune microenvironment of HCC, and its molecular mechanisms in metabolic dysfunction associated steatohepatitis (MASH) and metabolic associated fatty liver disease (MAFLD)-related HCC. Additionally, as a serum biomarker for HCC, diagnostic and prognostic value of GDF15 for HCC is summarized. The article elaborates on the immunological effects of GDF15, elucidating its effects on hepatic stellate cells (HSCs), liver fibrosis, as well as its role in HCC metastasis and tumor angiogenesis, and its interactions with anticancer drugs. Based on the impact of GDF15 on the immune response in HCC, future research should identify its signaling pathways, affected immune cells, and tumor microenvironment interactions. Clinical studies correlating GDF15 levels with patient outcomes can aid personalized treatment. Additionally, exploring GDF15-targeted therapies with immunotherapies could improve anti-tumor responses and patient outcomes.Keywords: growth differentiation factor 15, GDF15, hepatocellular carcinoma, HCC, immune suppression, immunotherapy
