Elevated Fas expression is related to increased apoptosis of circulating CD8+ T cell in patients with gastric cancer.
BACKGROUND
Extensive apoptosis of immune cells occurs in patients with cancer, and is possibly related to immune evasion by cancer cells. The present study was designed to investigate the correlation between apoptosis levels and Fas expression in CD8+ T lymphocytes in patients with gastric cancer.


METHODS
The expression of apoptosis markers (annexin V binding and caspase-3 activation) and the death receptor Fas in CD8+ T cells was evaluated by multicolor flow cytometry. Soluble Fas ligand (sFasL) in the sera was quantitated by enzyme-linked immunosorbent assay.


RESULTS
In patients with gastric cancer, 18.7% +/- 10.5% (mean +/- SD) of CD8+ T cells bound annexin V compared with 11.7% +/- 7.9% in normal controls (P = 0.0282). Fas expression in CD8+ T cells was higher in patients with gastric cancer (69.2% +/- 15.3%) than normal controls (50.6% +/- 15.3%) (P = 0.0051). The proportion of apoptotic CD8+ T cells was significantly correlated with Fas expression in CD8+ T cells (r = 0.409, P = 0.0214). In patients, Fas+CD8+ T cells preferentially underwent apoptosis and showed high caspase-3 activation. Moreover, the proportion of apoptotic CD8+ T cells was inversely correlated with serum levels of soluble Fas ligand (r = -0.324, P = 0.0359). Fas expression in tumor infiltrating CD8+ T cells was significantly more frequent (80.3% +/- 13.4%) than in circulating CD8+ T cells (67.9% +/- 15.5%) (P = 0.0046). A decrease in the percentage of Fas+CD8+ T cells was observed after surgery (54.1% +/- 12.8%) compared with before surgery (65.9% +/- 17.0%) (P = 0.0284).


CONCLUSIONS
The data indicate that up-regulation of Fas expression in CD8+ T cells is related to increased apoptosis of circulating CD8+ T cells in patients with gastric cancer. Further investigations into the detailed mechanism of apoptosis induction in Fas-positive CD8+ T cells are urgently required.
Department of Surgery, Division of Surgical Oncology, Tottori University School of Medicine, Yonago, Japan.
Toshiaki
T
Yoshikawa
Hiroaki
H
Saito
Tomohiro
T
Osaki
Sachiko
S
Matsumoto
Shunichi
S
Tsujitani
Masahide
M
Ikeguchi
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D019014:fas Receptor; D053148:Caspase 3