Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Abstract

Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.

Case report: Thyroid metastasis from hepatocellular carcinoma: a rare case with diffuse solid occupancy and unusual imaging findings

“…Recent analyses suggest that immune checkpoint inhibitors like pembrolizumab and nivolumab have shown effectiveness in patients with advanced HCC who have shown progression on sorafenib therapy or have an intolerance to it ( 34 ). These pharmaceuticals target vascular endothelial growth factor (VEGF) receptors and other angiogenesis-oriented pathways integral to the proliferation and metastatic dissemination of tumors ( 35 ). Immunotherapeutic avenues might wield more potential in treating metastatic HCC compared to conventional palliative surgical interventions.…”

Hepatocellular Carcinoma: Beyond the Border of Advanced Stage Therapy

“…Combination therapy using ICIs is a successful HCC therapy method. PD-1 and CTLA-4 are inhibitory immune checkpoints present on activated T cells and have been proposed as targets for HCC therapy [ 101 ]. Several ICIs such as pembrolizumab and nivolumab target PD-1, while atezolizumab and durvalumab target PD-L1.…”

Immunotherapy Based on Immune Checkpoint Molecules and Immune Checkpoint Inhibitors in Gastric Cancer–Narrative Review

“…The mechanism of action of ICIs is shown in Figure 3 . Their natural role is to prevent the immune system from overreacting and to maintain homeostasis during antimicrobial and antiviral responses [ 37 ]. The vast majority of well-known and effectively targeted ICPMs are expressed by T cells, but the cells of the innate immune system can also contribute, underscoring the complex nature of the process [ 38 ].…”