Immune Indicator Changes in Hepatocellular Carcinoma Undergoing TACE Plus ICIs and Anti-VEGF Antibodies/TKIs: A Prognostic Biomarker Analysis

Xiao-Yang Xu,&ast; Ze Wang,&ast; Chen-You Liu,&ast; Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Street, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comObjective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5– 32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3−CD19+ (p=0.004), CFB (p=0.027), NLR (p< 0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.Keywords: immune indicator, TACE, immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor microenvironment