A Reversible Defect in Natural Killer T Cell Function Characterizes the Progression of Premalignant to Malignant Multiple Myeloma

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2003 Jun 11

PMID 12796469

Citations 188

Authors

Madhav V Dhodapkar

Matthew D Geller

David H Chang

Kanako Shimizu

Shin-Ichiro Fujii

Kavita M Dhodapkar

Joseph Krasovsky

Affiliations

Soon will be listed here.

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. V alpha 24+V beta 11+ 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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