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Evaluation of the Function of Human Invariant NKT Cells from Cancer Patients Using -Galactosylceramide-Loaded Murine Dendritic Cells¹

Kanako Shimizu^*, Michihiro Hidaka, Norimitsu Kadowaki, Noriko Makita^*, Naoko Konishi^*, Koji Fujimoto, Takashi Uchiyama, Fumio Kawano, Masaru Taniguchi and Shin-ichiro Fujii^2,*

^* Research Unit for Cellular Immunotherapy, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan; Institute for Clinical Research, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan

NKT cells play a role in immunological regulation of certain diseases, and their frequency and/or function may be related to disease prognosis. However, it is often difficult to evaluate NKT cell function in patients with malignancies due to reduced numbers of NKT cells as well as the dysfunction of the APCs used as stimulators. We found that NKT cell function could not be evaluated by conventional ELISPOT assays, confirming the impaired function of APCs in chronic myelogenous leukemia (CML)-chronic phase patients. To overcome this problem, we have established a sensitive assay using murine dendritic cells to evaluate the function of small numbers of human NKT cells independent of autologous APCs. We found that imatinib-treated CML-chronic phase patients showing a complete cytogenetic response had NKT cells capable of producing IFN-, whereas NKT cells from patients who were only partially responsive to imatinib treatment did not produce IFN-. Functional NKT cells found in imatinib-treated, CML-complete cytogenetic response patients may offer the promise of effective immunotherapy with ex vivo-generated -galactosylceramide-pulsed dendritic cells. This new approach should be available for evaluating the functions of NKT cells and APCs in cancer patients.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Kanae Foundation for Life and Socio-Medical Science (to K.S.); the Japanese Clinical Oncology Fund and the Mitsubishi Research Foundation (to S.F.); and the Program for Promotion of Fundamental Studies in Healthy Sciences of the National Institute of Biomedical Innovation (to M.T.).

² Address correspondence and reprint requests to Dr. Shin-ichiro Fujii, Leader of Research Unit for Cellular Immunotherapy, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, 230-0045 Japan. E-mail address: fujiis{at}rcai.riken.jp

³ Abbreviations used in this paper: DC, dendritic cell; -GalCer, -galactosylceramide; DC/Gal, -GalCer-loaded DC; PB, peripheral blood; CML, chronic myelogenous leukemia; CP, chronic phase; CCR, complete cytogenetic response; PR, partial response; SFC, spot-forming cell; BM, bone marrow; LDA, limiting dilution assay; xeno-DC, xenogeneic DC; auto-DC, autologous DC; allo-DC, allogeneic DC.