Purpose: This study investigated the dynamic changes in circulating immune cells following immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), and interventional therapy in hepatocellular carcinoma (HCC).

Methods: HCC patients undergoing transarterial chemoembolization (TACE), TKI, and ICI treatment were included in the treatment group. Peripheral blood samples were collected from these patients before each cycle of PD-1 blockade treatment. Flow cytometry analysis was conducted to assess the composition of peripheral immune cells and identify PD-1-expressing T cells.

Results: The treatment group showed a median time-to-tumor progression (TTP) of 8 months and an overall survival (OS) of 19 months. In comparison, the control group had 6 months and 15 months respectively. These differences were statistically significant (P = 0.029 for TTP and P = 0.020 for OS). In HCC patients receiving Lenvatinib, more circulating natural killer (NK) cells were noted. After 1–2 cycles of PD-1 antibody treatment, a general decline in the proportion of circulating PD-1⁺T cells was found, indicating individual variations in response.

Conclusion: Circulating immune cells have the potential to serve as indicators of the response to immunotherapy, providing a means to monitor dynamic changes and optimize treatment for HCC.