At diagnosis,diffuse large B‐cell lymphoma patients show impaired rituximab‐mediated NK‐cell cytotoxicity |
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Authors: | Anne Danielou‐Lazareth Guylaine Henry Daniela Geromin Zena Khaznadar Josette Briere Ryad Tamouza Jean‐Michel Cayuela Catherine Thieblemont Antoine Toubert Nicolas Dulphy |
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Institution: | 1. Assistance Publique–H?pitaux de Paris (AP–HP), H?pital Saint‐Louis, Service d'Hématologie‐Oncologie Adulte, , Paris, France;2. Laboratoire d'Immunologie et Histocompatibilité, H?pital Saint‐Louis, AP–HP, , Paris, France;3. Laboratoire d'Hématologie Biologique, H?pital Saint‐Louis, AP–HP, , Paris, France;4. Saint‐Louis Hospital's Tumor Biobank, AP–HP, , Paris, France;5. Institut National de la Santé et de la Recherche Médicale (INSERM), , UMR‐S940 Paris, France;6. Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, , Paris, France;7. Laboratoire d'Anatomie Pathologique, H?pital Saint‐Louis, AP‐HP, , Paris, France;8. INSERM, , UMR‐S728 Paris, France |
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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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Keywords: | CD137 CD16 diffuse large B‐cell lymphoma innate immunity NK cell |
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