Immunophenotypes and cytotoxic functions of lymphocytes in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia. Immunological mechanisms are thought to play an important role in the control of tumor progression. The immune responses in HCC patients are poorly understood. In the present study, the proliferation and cytotoxic functions of lymphocytes from tumor tissues and peripheral blood of HCC patients were analysed. Simultaneously, the microcultures were phenotyped in order to determine the involvement of different lymphocyte subsets in mediating the cytotoxic function.

The frequencies of proliferating and cytotoxic lymphocytes from three tumor tissues and peripheral blood from ten HCC patients and nine healthy individuals were assessed by limiting dilution microculture analysis. These microcultures were phenotyped by single and dual color flow cytometry using monoclonal antibodies specific for CD4, CD8, CD56 and HLA-DR markers.

The precursor frequencies of both proliferating and cytotoxic lymphocytes were found to be comparable in the peripheral blood of HCC patients and healthy individuals. Compared to peripheral blood, a marked reduction in the precursor frequencies of proliferating and cytotoxic lymphocytes was observed in the tumor tissues of HCC patients. In the tumor tissues, a significantly higher frequency of cytotoxic T cells compared to natural killer cells was observed. Dual color flow cytometric analysis revealed increased percentages of CD8+ HLA-DR+ lymphocytes compared to CD4+ HLA-DR+ cells in the tumor tissues.

Our results suggest that depressed immune responses at the tumor site might be responsible for the escape of tumor cells from the immune surveillance of the host.