Interleukin-21 and rituximab enhance NK cell functionality in patients with B-cell chronic lymphocytic leukaemia.

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BlankInterleukin-21 and rituximab enhance NK cell functionality in patients with

B-cell chronic lymphocytic leukaemia.

CW Eskelund, L Nederby, AH Thysen, A Skovbo, AS Roug, and ME Hokland

Leuk Res, February 25, 2011; .

Institute of Medical Microbiology and Immunology, Aarhus University, Aarhus,

Denmark.

We have examined natural killer (NK) cell functionality of 54 B-CLL patients

upon in vitro stimulation with interleukin-21 (IL-21), together with the

anti-CD20 antibody, rituximab. Upon stimulation with rituximab-coated target

cells IFN-? production was reduced in patients' NK cells compared to healthy

donors', while both natural- and antibody-dependent cytotoxicity (ADCC) was

normal. Following additional stimulation with IL-21, IFN-? production, natural

cytotoxicity and ADCC were significantly augmented in patients. A complete

restoration of IFN-? production, however, required the depletion of malignant

cells prior to stimulation. Collectively, our data show that NK cells of B-CLL

patients are reversibly inhibited, but that their functionality can be

normalized by stimulation with IL-21 and when inhibitory effects of the

malignant B-CLL cells are eliminated by depletion.

PMID: 21354618