| Background & Objective: Argon-helium cryosurgical ablation (CSA), serving as a new cryosurgical approach, is a kind of mini-invasive surgical therapy, which is able to induce the necrosis of tumor cells through the formation of extracellular and intracellular ice crystals and then cell dehydration on the basis of rapidly freezing (<-140℃) as well as rapidly thawing (20-40℃) tumor tissues with argon/helium gas. Therefore, Argon-helium cryosurgical ablation becomes one of the major therapeutic approach for unresectable primary HCC patients at the middle and advanced satges. Boosting host anti-tumor immune response is alternative way for tumor disease. Recent studies have revealed that large amounts of resident regulatory T cells within tumor can inhibit the anti-tumor role via suppressing or killing effector CD4~+ or CD8~+T cells. Previous study has demonstrated that elimination of regulatory T cells can improve host anti-tumor immunity in tumor-bearing rat. Our findings indicate that high frequency of regulatory T cells correlates with poor prognosis in HCC patients. This study attempts to investigate how Argon-helium cryosurgical ablation influence regulatory T cells in HCC patients for evaluation of the prognosis in these patients .Methods: The frequence of regulatory T cells in 101 HCC patients' peripheral blood was evaluated with flow cytometery.The frequency and function of regulatory T cells in peripheral blood of 31 HCC patients were longitudinally evaluated before and after cryoablation. Statistical analysis was used to figure out the association of regulatory T cells with serum AFP level. The distribution of resident CD4~+, CD8~+ T cells and FoxP3~+ T cells in liver tissue of HCC patients was examined by using immunochemical staining.Results: Our study found that (1) There was a increased frequency of regulatory T cells in parallel with the disease progression in HCC patients (early stage: 6.89±1.27%; intermediate stage:9.13±1.36%; advanced stage: 10.32±2.04%; terminal stage:13.4±2.81%) . (2) The frequency of regulatory T cells was reduced in 17 responders of 31 HCC patients with cryoablation treatment. In addition, while seven serum AFP positive (>20ng/mL) patients simultaneously exhibited a decrease of serum AFP level. However, we found that there was a increased regulatory T cells in peripheral blood of 14 advanced stage patients following the cryoablation, among them, 9 AFP positive patients were with a increase in serum AFP level. (3) Regulatory T cells of HCC patients were found to suppress proliferation of PBMCs of healthy donors. (4) There is decreased tumor resident CD8~+, CD4~+ T and FoxP3~+ T cells in HCC patients compared with their counterparts at baseline, together with more decrease of FoxP3~+/CD8~+ T cell ratio than those before treatment.Conclusions: Our findings suggest that Argon-helium cryosurgical ablation affect the variation of regulatory T cells, which may favor to boost host anti-tumor immunity and indicate the prognosis of the disease. |
