Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas
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T Saibara1, T Maeda, M Miyazaki
1First Department of Medicine, Kochi Medical School, Nankoku, Japan.
Abstract:
We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.
Insights
Defective lymphokine-activated killer (LAK) activity is common in early hepatocellular carcinoma (HCC), but not due to low gamma-interferon production. Tumor burden, not impaired gamma-interferon, likely causes immune dysfunction in HCC.
Area of Science:
- Immunology
- Hepatology
- Oncology
Background:
- Previous studies indicated depressed gamma-interferon (IFN-γ) production and impaired lymphokine-activated killer (LAK) and natural killer (NK) activity in patients with large hepatocellular carcinoma (HCC).
- The exact mechanism linking IFN-γ and LAK activity in HCC remained unclear due to concurrent defects in advanced stages.
Purpose of the Study:
- To assess immune parameters, specifically LAK activity and IFN-γ production, in patients with small HCC (less than 2 cm).
- To investigate the underlying mechanism of immune dysfunction in early-stage HCC and its progression.
Main Methods:
- Immune parameters (LAK activity and IFN-γ production) were evaluated in 48 patients with small HCC.
- Surgical treatment was performed on 31 patients, with immune parameters monitored for 6 months post-surgery.
Main Results:
- A significant proportion of patients (64.6%) exhibited defective LAK activity.
- Conversely, defective IFN-γ production was rare (2.1%), challenging the hypothesis of IFN-γ deficiency as the primary defect.
- Post-surgical recovery of LAK activity in patients with initially low levels suggests tumor burden as a cause of immune impairment.
Conclusions:
- Defective LAK activity is prevalent in early HCC, independent of impaired IFN-γ production.
- These findings suggest that tumor burden, rather than a primary IFN-γ defect, contributes to immune dysfunction in HCC.
- This provides new insights into the mechanisms driving immune evasion and progression in hepatocellular carcinoma.