Immunotherapy for hepatocellular carcinoma[1]

Hepatocellular carcinoma (HCC) is a rapidly progressing and highly lethal tumor worldwide, often associated with chronic liver disease. While treatment options such as curative resection, liver transplantation, trans-arterial chemoembolization, radioembolization, radiofrequency ablation, and chemotherapy exist for HCC, their effectiveness is limited and they may worsen the underlying liver condition, offering little benefit to a significant number of patients with advanced HCC.

The treatment landscape for hepatocellular carcinoma (HCC) has been significantly transformed by recent advancements in immunotherapy and combination therapies. Ongoing clinical studies are continuously progressing to further enhance treatment options. Immunotherapy has demonstrated the potential to improve survival rates and achieve long-term cancer control in specific subsets of HCC patients, while also reducing the occurrence of adverse effects. Exploring the combination of immunotherapy with existing treatments for early and intermediate stages of HCC holds promise for a broader range of patients. Continued research into various markers, including programmed cell death-1/programmed cell death ligand 1, tumor mutational burden, circulating tumor DNA, microsatellite stability, DNA mismatch repair, neutrophil/lymphocyte ratio, cytokines, and peripheral immune response, aims to identify the most reliable indicators for selecting and sequencing systemic treatments, ultimately leading to optimal outcomes for HCC patients.

To date, the FDA has granted approval for seven immune checkpoint inhibitors (ICIs) that specifically target programmed cell death protein-1 (PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), or programmed cell death-ligand 1 (PD-L1) proteins. Additionally, there are other promising immunotherapeutic strategies, such as chimeric antigen receptor (CAR) T-cell therapy, adoptive cell treatment utilizing modified immune cells, customized cytokines, and cancer vaccines, which are nearing readiness and offer renewed optimism for patients with hepatocellular carcinoma (HCC).

PD-1 inhibitor

Nivolumab (Opdivo)        

Pembrolizumab (Keytruda)

Tislelizumab (Tevimbra)

PD-L1 inhibitor

Atezolizumab (Tecentriq)

Durvalumab (Imfinzi)

CTLA-4

Ipilimumab (Yervoy)

Tremelimumab (Imjudo)

Mandlik DS, Mandlik SK, Choudhary HB. Immunotherapy for hepatocellular carcinoma: Current status and future perspectives. World J Gastroenterol. 2023 Feb 14;29(6):1054-1075. doi: 10.3748/wjg.v29.i6.1054. PMID: 36844141; PMCID: PMC9950866.