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Göteborgs universitets publikationer

Reactive oxygen species induced by therapeutic CD20 antibodies inhibit natural killer cell-mediated antibody-dependent cellular cytotoxicity against primary CLL cells

Författare och institution:
Olle Werlenius (Sahlgrenska Cancer Center); Johan Aurelius (Sahlgrenska Cancer Center); Alexander Hallner (Sahlgrenska Cancer Center); Aliasghar Akhiani (Sahlgrenska Cancer Center); Maria Simpanen (Sahlgrenska Cancer Center); Anna Martner (Sahlgrenska Cancer Center); Per-Ola Andersson (-); Kristoffer Hellstrand (Sahlgrenska Cancer Center); Fredrik B Thorén (Sahlgrenska Cancer Center)
Publicerad i:
Oncotarget, 7 ( 22 ) s. 32046-32053
ISSN:
1949-2553
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Cancer och onkologi
Nyckelord:
monoclonal antibodies, reactive oxygen species, immunotherapy, NK cells, NOX2, chronic lymphocytic-leukemia, nk cells, hydrogen-peroxide, suppressor-cells, b-cells, t-cell, apoptosis, monocytes, death, polymorphism
Postens nummer:
240081
Posten skapad:
2016-08-10 10:44

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