α-Glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes obtained from cancer patients by activating CD3^-CD56⁺ NK cells in vitro

α-Glycosylceramides, such as α-galactosylceramide and α- glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, Vα14 TCR⁺NK1.1⁺ T cells, which accumulate preferentially in the liver, are considered to play a key role in the induction of antitumor immunity by α-glycosylceramides. We recently reported that Vα24 TCR⁺ NKT cells, the human homologues of murine Vα14 TCR⁺NK1.1⁺ cells, are rarely seen among freshly isolated human hepatic lymphocytes. Therefore, it is important to examine whether α- glycosylceramides also enhance the antitumor cytotoxicity of human hepatic lymphocytes, as they have been shown to do in murine systems, to determine the usefulness of α-glycosylceramides in cancer immunotherapy in humans. Here, we show that α-glycosylceramides greatly enhance the cytotoxicity of human hepatic lymphocytes obtained from cancer patients against the tumor cell lines, K562 and Colo201, in vitro. The direct effector cells of the elicited cytotoxicity were CD3^-CD56⁺ NK cells. Even though Vα24 TCR^-NKT cells proliferated remarkably in response to α-glycosylceramides, they did not contribute directly to the cytotoxicity. Our observations strongly suggest the potential usefulness of α-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3^-CD56⁺NK cells in the liver.