At diagnosis, diffuse large B-cell lymphoma patients show impaired rituximab-mediated NK-cell cytotoxicity

Authors

  • Anne Danielou-Lazareth,

    1. Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Saint-Louis, Service d'Hématologie-Oncologie Adulte, Paris, France
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  • Guylaine Henry,

    1. Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, AP–HP, Paris, France
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  • Daniela Geromin,

    1. Laboratoire d'Hématologie Biologique, Hôpital Saint-Louis, AP–HP, Paris, France
    2. Saint-Louis Hospital's Tumor Biobank, AP–HP, Paris, France
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  • Zena Khaznadar,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
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  • Josette Briere,

    1. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
    2. Laboratoire d'Anatomie Pathologique, Hôpital Saint-Louis, AP-HP, Paris, France
    3. INSERM, Paris, France
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  • Ryad Tamouza,

    1. Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, AP–HP, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
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  • Jean-Michel Cayuela,

    1. Laboratoire d'Hématologie Biologique, Hôpital Saint-Louis, AP–HP, Paris, France
    2. Saint-Louis Hospital's Tumor Biobank, AP–HP, Paris, France
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  • Catherine Thieblemont,

    1. Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Saint-Louis, Service d'Hématologie-Oncologie Adulte, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
    3. INSERM, Paris, France
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  • Antoine Toubert,

    1. Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, AP–HP, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
    3. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
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  • Nicolas Dulphy

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
    • Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, AP–HP, Paris, France
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Full correspondence Dr. Nicolas Dulphy, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1, avenue Claude Vellefaux, 75475 Paris Cedex 10, France

Fax: +33-142494641

e-mail: nicolas.dulphy@univ-paris-diderot.fr

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in adults. It is generally treated by a combination of chemotherapy and CD20-specific mAbs, such as rituximab, which act, at least partially, by activating antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC involves NK cells, particularly the CD56dim NK-cell subset expressing CD16, the low affinity Fcγ receptor. Here, we show that CD16 expression levels are decreased in a cohort of 36 newly diagnosed DLBCL patients compared with those in 20 healthy controls (HCs). CD137, a co-stimulatory molecule expressed on activated NK cells, was also expressed at lower levels in patients compared with controls. Cells sampled from our cohort also showed severely reduced degranulation activity when challenged with rituximab-coated tumor cells, which could not be corrected by stimulation with high doses of IL-2. These results suggest that rituximab-induced NK-cell ADCC could be defective in some DLBCL patients at diagnosis. These patients should be closely monitored and attempts made to improve their NK-cell function.

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