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-Glycosylceramides Enhance the Antitumor Cytotoxicity of Hepatic Lymphocytes Obtained from Cancer Patients by Activating CD3-CD56+ NK Cells In Vitro
*
Department of Research, Japanese Red Cross Central Blood Center, Tokyo, Japan;
Department of Surgery, Division of Surgical Oncology, University of Tokyo, Tokyo, Japan;
Pharmaceutical Research Laboratory, Kirin Brewery, Gunma, Japan; and
§
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
-Glycosylceramides, such as -galactosylceramide and
-glucosylceramide, induce antitumor immunity in various murine
cancer models. In the murine hepatic metastasis model, V14
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 -glycosylceramides. We recently
reported that V24 TCR+ NKT cells, the human homologues
of murine V14 TCR+NK1.1+cells, are rarely
seen among freshly isolated human hepatic lymphocytes. Therefore, it is
important to examine whether -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
-glycosylceramides in cancer immunotherapy in humans. Here, we show
that -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 V24 TCR+NKT cells proliferated
remarkably in response to -glycosylceramides, they did not
contribute directly to the cytotoxicity. Our observations strongly
suggest the potential usefulness of -glycosylceramides for
immunotherapy of liver cancer in humans based on their ability to
activate CD3-CD56+ NK cells in the
liver.
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