title: At diagnosis, diffuse large B-cell lymphoma patients show impaired rituximab-mediated NK-cell cytotoxicity.
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 CD56(dim) 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.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Service d'Hématologie-Oncologie Adulte, Paris, France.
authors: Anne
authors: A
authors: Danielou-Lazareth
authors: Guylaine
authors: G
authors: Henry
authors: Daniela
authors: D
authors: Geromin
authors: Zena
authors: Z
authors: Khaznadar
authors: Josette
authors: J
authors: Briere
authors: Ryad
authors: R
authors: Tamouza
authors: Jean-Michel
authors: JM
authors: Cayuela
authors: Catherine
authors: C
authors: Thieblemont
authors: Antoine
authors: A
authors: Toubert
authors: Nicolas
authors: N
authors: Dulphy
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D000069283:Rituximab; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007376:Interleukin-2; D017452:Receptors, IgG; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000069283:Rituximab