Expression of Fas antigen (CD95) in peripheral blood lymphocytes and in liver-infiltrating, cytotoxic lymphocytes in patients with hepatocellular carcinoma

Background. Fas-expressing cytotoxic T lymphocytes (CTLs) are important ant itumor immune effector cells in patients with hepatocellular carcinoma (HCC ). The role of transforming growth factor beta1 (TGF-beta1) in modulating t he expression of Fas by CTLs is not known in HCC. The objectives of this st udy were to characterize the expression of Fas by CTLs and natural killer ( NK) cells among peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in patients with HCC and to correlate the association, i f any, with serum TGF-beta1 levels. Methods. PBLs from 18 patients with HCC and TILs from 5 HCC liver specimens were isolated, and Fas expression was analyzed by three-color flow cytomet ry. The results were compared with results from normal control volunteers ( n=19 individuals). Serum TGF-beta1 levels in patients with HCC were measure d by enzyme-linked immunosorbent assay. Results. The median percentage of Fas expression by CD3 positive T cells wa s significantly higher in patients with HCC compared with normal controls ( 54.37% vs. 32.03%, respectively; P=0.0036), and this was attributable solel y to Fas expression by CD4 positive PBLs (54.46% vs. 34.90%, respectively; P=0.0234). In contrast, Fas expression was significantly higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK cells, and n atural T cells) compared with controls (all P values were < 0.001). Tumor s ize was inversely proportional to the TGF-<beta>1 levels (correlation coeff icient [r] = -0.725; P<0.0001), which were correlated inversely with Fas ex pression by CD4 positive PBLs (r = -0.516; P=0.01). Conclusions. In patients with HCC, TILs exhibit significantly increased exp ression of Fas compared with PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors were associated with lower serum TGF<be ta>1 levels, and this was correlated with greater Fas expression by CD4 pos itive PBLs. Cancer 2001; 92:2136-41. (C) 2001 American Cancer Society.