Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 197, Issue 12, Pages 1667-1676Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021650
Keywords
multiple myeloma; NKT cells; dendritic cells; interferon-gamma; immunotherapy
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Funding
- NCI NIH HHS [CA84512, P01 CA084512, CA81138] Funding Source: Medline
- NCRR NIH HHS [M01 RR000102, M01-RR00102] Funding Source: Medline
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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. Valpha24(+)Vbeta11(+) 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-gamma production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, alpha-galactosylceramide (alpha-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.
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