Correlation of dynamic alteration of regulatory T cells with the genesis and development of intrahepatic cholangiocarcinoma in a rat model

Abstract

Objective To investigate the correlation of dynamic alteration of regulatory T cells(Tregs) with the genesis and development of intrahepatic cholangiocarcinoma in a rat model. Methods A total of 40 male SD rats were administered orally with drinking water containing 300 mg/L thioacetamide, and 40 rats administered normally as control group. Peripheral blood mononuclear cells(PBMCs) ,spleen, tumor and liver were harvested and detected at a two-weeks interval from 10 weeks after initiation of thioacetamide. Tregs in PBMCs and spleen were examined by flow cytometry, and those in tumor microenvironment by immunohistochemistry. Results(1) The main pathologic features in different phases were observed as follows:hyperplasia of duct gland from 12th to 14th week;atypical hyperplasia at 16th week;the visible tumor after 18th week.(2) In PBMCs,an increasing proportion of Tregs was observed from the 14th week [(4.25±0. 64) % vs(3. 76±0. 60) % , P<0.01 ]. The proportion of Tregs reached the peak at 18th week [(6.18±0.64)% ]. Tregs in the spleen began to increase at 18th week,reached the peak at 20th week [(8.54±0.36)% ].(3) A significant increase of Tregs was examined at 18th week in tumor microenvironment(P<0.05). With the progress of tumor,the number of Tregs in tumor microenvironment was increased. Conclusion The increased Tregs in PBMCs and the spleen were related to tumor genesis. But they did not show any correlation with tumor progression. The proportion of Tregs in tumor microenvironment was correlated with tumor progression. Key words: Cholangiocarcinoma; Model,animal; T cells