Mechanism of liposome arsenic trioxide regulating tumor microenvironment and sensitizing tumor immune response after radiofrequency ablation.

OBJECTIVE

We hypothesized that preoperative administration of liposome arsenic trioxide (LATO) would downregulate hypoxia-inducible factor-1α (HIF-1α) in residual tumors following incomplete radiofrequency ablation (iRFA), thereby modulating the tumor microenvironment, suppressing residual tumor proliferation and angiogenesis, and consequently enhancing the antitumor efficacy of programmed death-ligand 1 (PD-L1) blockade.

METHODS

Using a murine Hepa1-6 hepatocellular carcinoma model subjected to incomplete radiofrequency iRFA, cohorts were stratified based on preoperative LATO administration and postoperative anti-PD-L1 antibody combination therapy, and the indexes such as proliferation and immune infiltration of residual tumor were tested respectively.

RESULTS

After iRFA, residual tumors exhibited significant up-regulation of PCNA, CD31, and HIF-1α compared with the control group (all p < 0.0001). Intravenous infusion of LATO before RFA could significantly decrease the expression of PCNA, CD31 and HIF-1α in the residual tumor, promote the infiltration of immune cells (CD4+, CD8+) and prolong the survival time of mice. After RFA, combined use of anti-PD-L1 antibody can further reduce the expression of cell proliferation and tumor proliferation.

CONCLUSION

Pre-treatment with LATO prior to RFA appears to modulate the tumor microenvironment, which may contribute to improved ablation efficacy and help restrain the progression of residual tumors. Furthermore, it could potentially enhance the antitumor effect of combining RFA with anti-PD-L1 antibody therapy by sensitizing the tumor immune response.