Blocking Tim-3 enhances CD8+ T cell activity to inhibit hepatocellular carcinoma recurrence post-radiofrequency ablation.

Abstract

Background: Incomplete radiofrequency ablation (iRFA) for hepatocellular carcinoma (HCC) during radiofrequency ablation (RFA) may result in rapid progression of residual tumors and resistance to anti-PD-1 therapy. Research has demonstrated elevated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in CD8⁺ T cells in the peripheral blood of patients with HCC after RFA, leading to a diminished anti-tumor immune response. Therefore, this study examined the effectiveness of anti-Tim-3 therapy in treating residual tumors after iRFA and explored the underlying mechanisms.

Methods: To examine the expression of Tim-3 in the residual tumors after iRFA for HCC in mice. Treat residual tumors with anti-αTim-3 and evaluate its efficacy. Transcriptomic sequencing was conducted on the residual tumors to explore the underlying mechanisms. Meanwhile, residual tumors were treated with a combination of anti-αTim-3 and anti-αPD-1 to evaluate efficacy.

Results: This study demonstrated elevated Tim-3 expression in CD8⁺ T cells within residual tumors after iRFA. CD8⁺ T cells exhibit attenuated anti-tumor immune responses associated with accelerated tumor progression. Treatment with anti-αTim-3 impeded the advancement of residual tumors by enhancing CD8⁺ T cell infiltration and stimulating their anti-tumor activities. Furthermore, anti-αTim-3 therapy upregulated PD-1 expression in residual tumors. Combination therapy involving anti-αTim-3 and anti-αPD-1 elicited a robust anti-tumor immune response.

Conclusions: Tim-3 expression is elevated in CD8⁺ T cells within residual tumors after iRFA, which contributed to their accelerated advancement. Anti-αTim-3 slows tumor progression by boosting CD8⁺ T cell anti-tumor activity and enhancing response to anti-αPD-1 treatment.