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

alpha-Glycosylceramides, such as alpha-galactosylceramide and alpha-glucosy lceramide, induce antitumor immunity in various murine cancer models. In th e murine hepatic metastasis model, V alpha 14 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 alpha-glycosylceramides. We recen tly reported that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14 TCR(+)NK1.1(+)cells, are rarely seen among freshly isolated hum an hepatic lymphocytes, Therefore, it is important to examine whether alpha -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 alpha-glycosylceramides in cancer immunotherapy in human s. Here, we show that alpha-glycosylceramides greatly enhance the cytotoxic ity 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 V alpha 24 TCR+NKT cells proliferated remarkably in response to alpha-glycosylceram ides, they did not contribute directly to the cytotoxicity. Our observation s strongly suggest the potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3-CD56+ NK cells in the liver.