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Keywords:

  • lymphokine-activated killer (LAK) activity;
  • natural killer (NK) activity;
  • prognostic marker;
  • survival

Abstract:

Transforming growth factor-β1 (TGF-β1) has been implicated in tumor progression. The relationship of this cytokine as measured in plasma to anti-tumor immunity and prognosis was investigated.

This study consisted of 70 consecutive patients with unresectable hepatocellular carcinoma (HCC) (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with HCC were divided into those with plasma TGF-β1 concentrations above (group A, n=21) or below (group B, n=49) 10 ng/ml (the mean concentration+2SD in the concentrations of the controls with cirrhosis was 8.7 ng/ml).

Age, gender, Child-Pugh grade, and tumor stage distributions were similar in groups A and B. Considering all tumor stages together and individually, group A had a significantly shorter survival (median for all stages, 2 months) than group B (median for all stages, 10 months; P<0.01, generalized Wilcoxon's test). Groups A and B had significantly shorter survival than controls with cirrhosis (P<0.001 for each). Lymphokine-activated killer (LAK) activity in group A was significantly lower than that in group B (P<0.001). Natural killer (NK) activity in group A was also significantly lower than that in group B (P<0.05). Plasma TGF-β1 concentration was a significant predictor of survival by Cox's proportional-hazards regression analysis (multivariate analysis, P<0.01). LAK and NK activities were also weak but significant predictors (P<0.05 and <0.05, respectively).

These data suggest that plasma TGF-β1 concentration is a predictor of outcome of patients with unresectable HCC. Circulating TGF-β1 supposedly contributes to the suppression of anti-tumor immunity in the advanced disease.