TLR-based therapeutic strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related deaths worldwide. Chronic inflammation and immune dysregulation, often driven by viral infections or metabolic disorders, play a significant role in its pathogenesis. Toll-like receptors (TLRs), key components of innate immunity, have emerged as important regulators in the progression of liver disease and tumorigenesis. This review aims to evaluate the role of TLR signaling in the development, progression, and therapeutic potential of HCC. While TLRs are mainly found on immune cells, they are also functionally expressed in various human cancers, including HCC. TLRs, such as TLR4, can either promote or inhibit tumor progression, depending on the cellular context and microenvironment. TLR polymorphisms, including TLR1 rs5743551 and TLR4 rs1927914, are associated with inflammation, infection risk, and cancer recurrence. Although preclinical studies support the use of TLR agonists to enhance immunotherapy, their clinical translation remains limited due to inconsistent patient responses. This might be due to the diverse effects these agonists exert on various cell types within the tumor microenvironment. Future research should focus on patient-specific TLR profiles, the development of improved biomarkers, and the combination of therapies to optimize outcomes. Understanding the dual role of TLRs could lead to more precise and effective HCC treatments.