A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma Journal Article

Authors: Dhodapkar, M. V.; Geller, M. D.; Chang, D. H.; Shimizu, K.; Fujii, S. I.; Dhodapkar, K. M.; Krasovsky, J.
Article Title: A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma
Abstract: We studied the function of antitumor T and natural killer T (NKT) cells from the blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive myeloma, or progressive multiple myeloma. We show that antitumor killer T cells can be detected in patients with both progressive or nonprogressive myeloma. Vα24 +Vβ11 + invariant NKT cells are detectable in the blood and tumor bed of all cohorts. However, freshly isolated NKT cells from both the blood and tumor bed of patients with progressive disease, but not nonprogressive myeloma or premalignant gammopathy, have a marked deficiency of ligand-dependent interferon-γ production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, α-galactosylceramide (α-GalCer). Fresh myeloma cells express CD1d, and can be efficiently killed by autologous NKT cells. We hypothesize that presentation of tumor derived glycolipids by myeloma cells leads to NKT dysfunction in vivo. These data demonstrate that clinical progression in patients with monoclonal gammopathies is associated with an acquired but potentially reversible defect in NKT cell function and support the possibility that these innate lymphocytes play a role in controlling the malignant growth of this incurable B cell tumor in patients.
Keywords: controlled study; unclassified drug; human cell; disease course; cancer growth; antigen expression; biological markers; cells, cultured; cell function; multiple myeloma; dendritic cell; cohort analysis; cancer cell culture; antigen presentation; dendritic cells; immunotherapy; gamma interferon; disease progression; natural killer cell; killer cells, natural; cytotoxicity, immunologic; t-lymphocyte subsets; monoclonal immunoglobulinemia; t lymphocyte subpopulation; alpha galactosylceramide; cd1d antigen; precancerous conditions; galactosylceramide; glycolipid; interleukin-4; precancer; paraproteinemias; myeloma cell; nkt cells; interferon type ii; antigens, cd1; interferon production; interferon-γ; gammopathy; humans; human; priority journal; article; tumor derived glycolipid; b cell tumor; nonprogressive myeloma; premalignant gammopathy; progressive multiple myeloma
Journal Title: Journal of Experimental Medicine
Volume: 197
Issue: 12
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2003-06-16
Start Page: 1667
End Page: 1676
Language: English
DOI: 10.1084/jem.20021650
PUBMED: 12796469
PROVIDER: scopus
PMCID: PMC2193955
Notes: Export Date: 12 September 2014 -- Source: Scopus
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