| Lenvatinib combined with immune checkpoint inhibitors (ICIs) has emerged as one of the pivotal systemic and conversion therapeutic strategies for unresectable, intermediate and advanced hepatocellular carcinoma (HCC). Remodeling of the tumor immune microenvironment (TIME) constitutes the core mechanism underlying their synergistic anti-HCC activity, and numerous novel research advances regarding mechanistic elucidation and clinical translation in this field remain to be comprehensively summarized. Focusing on the drivers of immunosuppressive TIME formation in HCC, this paper systematically reviews the dynamic remodeling effects exerted by lenvatinib plus ICIs on HCC TIME, including facilitating tumor vascular normalization, alleviating tissue hypoxia, reversing metabolic reprogramming, and dynamically rearranging immune cell populations. Meanwhile, efficacy data from multiple pivotal clinical trials are systematically analyzed to discuss the merits and limitations of this combination regimen in real-world clinical practice, thereby providing evidence-based references for individualized precise prevention and treatment as well as basic translational research of HCC. |
