Advances in Immunotherapy for Hepatocellular Carcinoma (HCC)
Overview
Affiliations
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths in the world. More than half of patients with HCC present with advanced stage, and highly active systemic therapies are crucial for improving outcomes. Immune checkpoint inhibitor (ICI)-based therapies have emerged as novel therapy options for advanced HCC. Only one third of patients achieve an objective response with ICI-based therapies due to primary resistance or acquired resistance. The liver tumor microenvironment is naturally immunosuppressive, and specific mutations in cell signaling pathways allow the tumor to evade the immune response. Next, gene sequencing of the tumor tissue or circulating tumor DNA may delineate resistance mechanisms to ICI-based therapy and provide a rationale for novel combination therapies. In this review, we discuss the results of key clinical trials that have led to approval of ICI-based therapy options in advanced HCC and summarize the ongoing clinical trials. We review resistance mechanisms to ICIs and discuss how immunotherapies may be optimized based on the emerging research of tumor biomarkers and genomic alterations.
TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma.
Guo H, Wang M, Ni C, Yang C, Fu C, Zhang X J Exp Clin Cancer Res. 2025; 44(1):20.
PMID: 39838454 PMC: 11748316. DOI: 10.1186/s13046-025-03287-w.
Ning L, Chen D, Han J, Xie G, Sun J Front Oncol. 2024; 14:1474496.
PMID: 39723378 PMC: 11668663. DOI: 10.3389/fonc.2024.1474496.
Wang J, Cao Y, Tian Y, Dai C, Jin T, Xu F Cancer Med. 2024; 13(22):e70419.
PMID: 39540362 PMC: 11561519. DOI: 10.1002/cam4.70419.
Hepatocellular Carcinoma Immunotherapy: Predictors of Response, Issues, and Challenges.
Rizzo A, Brunetti O, Brandi G Int J Mol Sci. 2024; 25(20).
PMID: 39456872 PMC: 11507510. DOI: 10.3390/ijms252011091.
New advances in the treatment of intermediate and advanced hepatocellular carcinoma.
Zhonghao J, Fan Y Front Oncol. 2024; 14:1430991.
PMID: 39376988 PMC: 11456399. DOI: 10.3389/fonc.2024.1430991.