Expression of Fas/FasL in CD8+ T and CD3+ Foxp3+ Treg Cells - Relationship with Apoptosis of Circulating CD8+ T Cells in Hepatocellular Carcinoma Patients

  • Guo, Cun-Li ;
  • Yang, Xiu-Hua ;
  • Cheng, Wen ;
  • Xu, Yi ;
  • Li, Jie-Bing ;
  • Sun, Yi-Xin ;
  • Bi, Yu-Mei ;
  • Zhang, Lei ;
  • Wang, Qiu-Cheng
  • Published : 2014.03.30


Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that $Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, $CD8^+T$ cells and $Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in $CD8^+T$ lymphocytes and $Foxp3^+T$ cells in patients with HCC. Methods: $CD8^+T$ cells and $CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in $CD8^+T$ cells and FasL in $CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in $CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of $CD8^+T$ cells binding annexin V and Fas expression in $CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic $CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with $CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of $CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in $Fas^+CD8^+T$ cells in vitro are required.


Hepatocellular carcinoma;$CD8^+T$ lymphocytes-$CD3^+Foxp3^+T$ cells;apoptosis;Fas;Fas ligand


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Supported by : China National Science Foundation