Evaluation of the function of human invariant NKT cells from cancer patients using alpha-galactosylceramide-loaded murine dendritic cells.
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-gamma, whereas NKT cells from patients who were only partially responsive to imatinib treatment did not produce IFN-gamma. Functional NKT cells found in imatinib-treated, CML-complete cytogenetic response patients may offer the promise of effective immunotherapy with ex vivo-generated alpha-galactosylceramide-pulsed dendritic cells. This new approach should be available for evaluating the functions of NKT cells and APCs in cancer patients.
Shimizu
Kanako
K
Research Unit for Cellular Immunotherapy, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Hidaka
Michihiro
M
Kadowaki
Norimitsu
N
Makita
Noriko
N
Konishi
Naoko
N
Fujimoto
Koji
K
Uchiyama
Takashi
T
Kawano
Fumio
F
Taniguchi
Masaru
M
Fujii
Shin-ichiro
S
D000818:Animals; D001549:Benzamides; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005699:Galactosylceramides / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001549:Benzamides; D005699:Galactosylceramides; D010879:Piperazines; D011743:Pyrimidines; C493154:alpha-galactosylceramide; D018664:Interleukin-12; D007371:Interferon-gamma; D000068877:Imatinib Mesylate