ASSESSMENT OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY AND GAMMA-INTERFERON PRODUCTION IN PATIENTS WITH SMALL HEPATOCELLULAR CARCINOMAS

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in p atients with relatively large hepatocellular carcinomas. These paramet ers were normal in cirrhosis. Some evidence had suggested a gamma-inte rferon production defect as the main cause of depressed lymphokine-act ivated killer activity in hepatocellular carcinoma, (i.e., gamma-inter feron enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer in duction). However, we were unable to clinically define the precise mec hanism operating here because gamma-interferon production and lymphoki ne-activated killer activity were both defective in advanced hepatocel lular carcinoma. In recent years, it has become possible to detect eve n small hepatocellular carcinomas on ultrasonography and to confirm th em by fine-needle biopsy. In this study, we assessed those immune para meters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mech anism of these defects. Lymphokine-activated killer activity was defec tive in 31 patients (64.6%), whereas gamma-interferon production was d efective in only 1 of these patients (2.1%). This observation argues a gainst the hypothesis that defective gamma-interferon production is th e primary defect and provides new insight into the mechanism of progre ssion of defective immune function in hepatocellular carcinoma. Thirty -one of the 48 hepatocellular carcinoma patients were treated surgical ly, and these immune parameters were followed for 6 mo. The recovery o f lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the t umor burden as the cause of defective lymphokine-activated killer acti vity.