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Neutrophils mediate antibody-induced antitumor effects in mice.

Abstract : Tumor engraftment followed by monoclonal antibody (mAb) therapy targeting tumor antigens represents a gold standard for assessing the efficiency of mAbs to eliminate tumor cells. Mouse models have demonstrated that receptors for the Fc portion of immunoglobulin G (FcγRs) are critical determinants of mAb therapeutic efficacy, but the FcγR-expressing cell populations responsible remain elusive. We show that neutrophils are responsible for mAb-induced therapy of both subcutaneous syngeneic melanoma and human breast cancer xenografts. mAb-induced tumor reduction, abolished in neutropenic mice, could be restored in FcγR-deficient hosts upon transfer of FcγR+ neutrophils or upon human FcγRIIA/CD32A transgenic expression. Finally, conditional knockout mice unable to perform FcγR-mediated activation and phagocytosis specifically in neutrophils were resistant to mAb-induced therapy. Our work suggests that neutrophils are necessary and sufficient for mAb-induced therapy of subcutaneous tumors, and represent a new and critical focal point for optimizing mAb-induced immunotherapies that will impact on human cancer treatment.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02513290
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Submitted on : Friday, March 20, 2020 - 2:42:43 PM
Last modification on : Monday, March 23, 2020 - 5:58:56 PM

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Marcello Albanesi, David Mancardi, Friederike Jönsson, Bruno Iannascoli, Laurence Fiette, et al.. Neutrophils mediate antibody-induced antitumor effects in mice.. Blood, American Society of Hematology, 2013, 122 (18), pp.3160-3164. ⟨10.1182/blood-2013-04-497446⟩. ⟨pasteur-02513290⟩

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