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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 3/2012

01-06-2012

Primary B-CLL Resistance to NK Cell Cytotoxicity can be Overcome In Vitro and In Vivo by Priming NK Cells and Monoclonal Antibody Therapy

Authors: Caroline Veuillen, Thérèse Aurran-Schleinitz, Rémy Castellano, Jérôme Rey, Françoise Mallet, Florence Orlanducci, Laurent Pouyet, Sylvaine Just-Landi, Diane Coso, Vadim Ivanov, Xavier Carcopino, Réda Bouabdallah, Yves Collette, Cyril Fauriat, Daniel Olive

Published in: Journal of Clinical Immunology | Issue 3/2012

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Abstract

Despite recent advances with monoclonal antibody therapy, chronic lymphocytic leukemia (CLL) remains incurable. Natural killer (NK) cells are potent antitumoral effectors, particularly against hematological malignancies. Defective recognition of B-CLL leukemic cells by NK cells has been previously described. Here, we deciphered the mechanisms that hamper NK cell-mediated clearance of B-CLL and evaluated the potential of NK cells as therapeutic tools for treatment of CLL. First of all, leukemic B cells resemble to normal B cells with a weak expression of ligands for NK receptors. Conversely, NK cells from B-CLL patients were functionally and phenotypically competent, despite a decrease of expression of the activating receptor NKp30. Consequently, resting allogeneic NK cells were unable to kill leukemic B cells in vitro. These data suggest that patients’ NK cells cannot initiate a proper immune reaction due to a lack of leukemic cell recognition. We next set up a xenotransplantation mouse model to study NK-CLL cell interactions. Together with our in vitro studies, in vivo data revealed that activation of NK cells is required in order to control B-CLL and that activated NK cells synergize to enhance rituximab effect on tumor load. This study points out the requirements for immune system manipulation for treatment of B-CLL in combination with monoclonal antibody therapy.
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Metadata
Title
Primary B-CLL Resistance to NK Cell Cytotoxicity can be Overcome In Vitro and In Vivo by Priming NK Cells and Monoclonal Antibody Therapy
Authors
Caroline Veuillen
Thérèse Aurran-Schleinitz
Rémy Castellano
Jérôme Rey
Françoise Mallet
Florence Orlanducci
Laurent Pouyet
Sylvaine Just-Landi
Diane Coso
Vadim Ivanov
Xavier Carcopino
Réda Bouabdallah
Yves Collette
Cyril Fauriat
Daniel Olive
Publication date
01-06-2012
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 3/2012
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-011-9624-5

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