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

Christian W Eskelund1, Line Nederby, Anna H Thysen

  • 1Institute of Medical Microbiology and Immunology, Aarhus University, and Department of Haematology, Aarhus University Hospital, Aarhus, Denmark. christianeskelund@gmail.com

Leukemia Research
|March 1, 2011
PubMed

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-γ 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-γ production, natural cytotoxicity and ADCC were significantly augmented in patients. A complete restoration of IFN-γ 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.