Effect of Transarterial Embolization Combined with Chemotherapy on Regulatory T Cells and Vascular Endothelial Growth Factor in the Tumor Immune Microenvironment of Intrahepatic Cholangiocarcinoma.

PURPOSE: To investigate whether transarterial embolization (TAE) and systemic gemcitabine + cisplatin (GC) modulates CD4+CD25+Foxp3+ regulatory T cells (Tregs) infiltration, a major immunosuppressive subset, and expression of vascular endothelial growth factor (VEGF), a critical proangiogenic molecule, in a thioacetamide-induced orthotopic intrahepatic cholangiocarcinoma (ICC) model using male Sprague-Dawley (SD) rats.

MATERIALS AND

METHODS

Twenty-four ICC-bearing SD rats were randomized into 4 groups (n = 6 per group). The control group received no treatment, whereas the GC group was given intraperitoneal injections of gemcitabine (200 mg/kg) plus cisplatin (8 mg/kg) on Days 0, 4, 8, and 12. The TAE group underwent hepatic artery embolization on Day 0, and the combination group received TAE on Day 0 followed by GC administration. Tumor volume was measured via computed tomography (CT) on Days -1, 7, and 14. Flow cytometry determined the proportion of Tregs among CD4+ T cells. Intratumoral Treg density is quantified by immunofluorescence. Immunohistochemistry detected VEGF expression. Statistical analysis used 1-way analysis of variance with appropriate post hoc tests.

RESULTS

There were no significant tumor volume differences within 14 days. TAE increased peripheral Treg proportion, whereas GC and combination therapy reduced it. The combination group had the lowest intratumoral Treg proportion (5.25% [SEM ± 0.76]). VEGF expression was elevated in the TAE group but suppressed in the combination group (8.68% [SEM ± 1.36] vs control, 18.37% [SEM ± 3.24]; P = .0140). All treatment groups showed reduced intratumoral Treg density compared with the control.

CONCLUSIONS

In a thioacetamide-induced orthotopic ICC rat model, TAE combined with systemic GC reduces intratumoral Treg infiltration and VEGF expression. These findings indicate that the combination therapy exerts superior immunomodulatory effects compared with TAE or GC monotherapy in rats.