The Change Of Peripheral Regulatory T Cells In Patients With Hepatocellular Carcinoma And Its Clinical Significance

ObjectiveHepatocellular carcinoma(HCC) is the fifth most common cancer worldwide with a poor prognosis.HCC is characterized by progressive development and poor prognosis, with less than 5%probability of 5-year survival.Chronic hepatitis B virus(HBV) infection is the established causative agent of primary HCC and contributes to more than 80%of HCC cases throughout the world.It is unclear why persistent inflammation in the liver fails to clear viral infection and leads to HCC in these patients.This study attempted to characterize CD4⁺CD25⁺forkhead/winged helix transcription factor (Foxp3)⁺ regulatory T cells(Tregs) in the blood of HCC patients.Method37 HCC patients with a homogeneous background of chronic HBV infection were enrolled in this study.HCC stage was evaluated according to the criteria for diagnosis and staging primary liver cancer constituted by the Chinese Anti-cancer Association in 2001.Blood samples were obtained from 16 liver cirrhosis(LC) patients all of which was a consequence of HBV.Control blood samples were also taken from 30 age-and sex-matched healthy blood donors.Then,the expression CD4,CD25,and FoxP3 in peripheral blood T cell were examined by flow cytometry.Flow cytometry was performed with a FACSCalibur(BD Biosciences) instrument and the data were analysed by using Cell Quest software.The percentage of CD4⁺CD25^high and CD4⁺CD25⁺FOXP3⁺ T cells was determined using three-color flow cytometry.The absolute numbers of CD4⁺CD25^high and CD4⁺CD25⁺FOXP3⁺ T cells were calculated based on the peripheral blood lymphocyte count at time of sampling.Differences in the level of CD4⁺CD25^high and CD4⁺CD25⁺FOXP3⁺ Tregs among the different groups of patients were analyzed. ResultThe frequencies of leukocyte,lymphocytes from LC patients receiving were lower than that from NC.There was no significantly different in peripheral leukocyte, lymphocytes and granulocyte between HCC patients and LC patients.The CD4⁺CD25^high population represents 1%to 4%of the CD4⁺ T cell population;however, CD4⁺CD25^low cells compromise 10%to 14%of CD4⁺ T cells.The frequency of CD4⁺CD25^high T cells in HCC patients was significantly higher than that in normal controls(P＜0.01),however there was no significantly different between HCC patients and LC patients(P＞0.05).There was a significantly higher number of circulating CD4⁺CD25⁺Foxp3⁺ T cells in HCC patients than in normal controls(P＜0.01),but not LC patients(P＞0.05).The increase of CD4⁺CD25^high/CD4⁺ was greater in patients at stageâ…¢than in patients at stageâ… andâ…¡.However,there was no significantly difference about CD4⁺CD25⁺Foxp3⁺/CD4⁺ at different stage in HCC patients.Conclusion1 Quantification of blood CD4⁺CD25⁺ and CD4⁺CD25⁺Foxp3⁺ Tregs may not help to decide the immune status of HCC,LC and NC.2.The level of blood CD4⁺CD25⁺ and CD4⁺CD25⁺Foxp3⁺ Tregs were decreased in HCC patients compared with normal controls.Tregs in human cancer might suppress tumor-specific immune responses.3.These T cells might prevent affective antitumor immune responses and be one of mechanisms that immune function was impaired in the patients with HCC.