Identification of prognostic tumor microenvironment in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors

Background: In advanced hepatocellular carcinoma (HCC), the triple combination therapy of hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has shown promise as a front-line treatment. This study aimed to explore the tumor microenvironment (TME) characteristics of the population benefiting most from this treatment. Methods: The study included 44 patients, with 38 ultimately receiving the HAIC + FOLFOX + lenvatinib + PD-1 inhibitor treatment. Tumor response was evaluated using modified RECIST criteria, classifying patients as responders (complete or partial response) or non-responders (stable or progressive disease). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed. Additionally, genetic sequencing and RNA analysis were conducted on biopsy samples to identify TME differences between the two groups. Results: Among the 38 patients, 22 responded favorably, showing significantly longer median OS (not-reached vs . 8.6 months) and median PFS (15.3 months vs . 2.0 months) compared to non-responders. Common AEs included AST elevation, stomachache, nausea, and hypertension, with limited severe AEs. Genetic analysis revealed no significant differences in DNA features between the groups. However, RNA analysis indicated that responders had a more robust immune status, better drug sensitivity, and increased immune cell infiltration. Notably, higher levels of tumor-infiltrating T lymphocytes were linked to better responses, longer PFS, and OS. Conclusion: The differences in the initial TME of patients, especially in tumor-infiltrating T lymphocytes, may be potential biomarkers for predicting response and prognosis. This finding provides clues to search for biomarkers for this triple combination therapy in advanced HCC.