Induction by OK-432 of lymphokine activated killer precursor cells in hepatocellular carcinoma

We investigated the question whether lymphokine-activated killer precursor (pre-LAK) cells are induced by OK-432 in vivo, in hepatocellular carcinoma (HCC). Ten patients with HCC were randomly divided into two groups. In group A (n = 5), OK-432 was pre-operatively administered via the hepatic artery. The group B patients (n = 5) served as controls. Tumor-infiltrating lymphocytes (TILs) were collected from the resected tumors. The cytotoxicity of TILs against natural killer (NK)-sensitive K562 cells and NK-insensitive Raji cells was examined by phenotypic analysis with flow cytometry. Freshly isolated TILs, whether treated with OK-432 or not, showed low cytotoxicity against both tumor cells. However, OK-432 pretreatment increased the T-lymphocyte population of TILs, particularly with interleukin-2 (IL-2) receptor positive cells. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, while untreated TILs showed no activation (P < 0.05). We postulate that pre-LAK cells are induced by OK-432 in TILs, mainly from the T-lymphocyte population. The possibility that LAK cells can be endogenously induced in HCC if OK-432 and rIL-2 are concomitantly administered needs to be considered for immunotherapy to HCC.