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

• Published in: European journal of immunology 2013-05, Vol.43 (5), p.1383-1388
• Main Authors: Danielou‐Lazareth, Anne, Henry, Guylaine, Geromin, Daniela, Khaznadar, Zena, Briere, Josette, Tamouza, Ryad, Cayuela, Jean‐Michel, Thieblemont, Catherine, Toubert, Antoine, Dulphy, Nicolas
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antineoplastic Agents - pharmacology; Case-Control Studies; CD137; CD16; Cell Degranulation - drug effects; Cell Degranulation - immunology; Cells, Cultured; Cytotoxicity; Cytotoxicity, Immunologic - drug effects; diffuse large B‐cell lymphoma; Gene Expression; GPI-Linked Proteins - genetics; GPI-Linked Proteins - immunology; Humans; Immune system; Immunity, Cellular - drug effects; Immunophenotyping; innate immunity; Interleukin-2 - pharmacology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - pathology; NK cell; Receptors, IgG - genetics; Receptors, IgG - immunology; Rituximab; Tumor Necrosis Factor Receptor Superfamily, Member 9 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 9 - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242733

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.