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Intravital Microscopy Identifies Macrophages as Effector Cells for Monoclonal Antibody Therapy of Cancer
Author(s) -
Egmond Marjolein
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.233.3
Subject(s) - monoclonal antibody , effector , immune system , cancer cell , macrophage , intravital microscopy , cancer research , antibody dependent cell mediated cytotoxicity , biology , cancer , microbiology and biotechnology , antibody , in vivo , immunology , in vitro , biochemistry , genetics
Monoclonal antibodies (mAbs) have become an important addition to chemo‐ and/or radiotherapy for the treatment of cancer. They can exert multiple effector functions that can lead to eradication of tumor in vitro , such as induction of apoptosis, growth inhibition, and initiation of complement‐dependent lysis. Furthermore, mAbs can recruit immune effector cells. To investigate how mAbs mediate tumor cell elimination in vivo , and to establish which effector cells are involved we performed live cell imaging as well as intravital microscopy. We show that antibody‐dependent phagocytosis (ADCP) by macrophages is a prominent mechanism to remove tumor cells from the circulation after mAb therapy. Tumor cells were rapidly recognized and arrested by liver macrophages (Kupffer cells) even in the absence of mAbs. Furthermore, tumor cells were sampled by Kupffer cells, which was however not sufficient for elimination. By contrast, anti‐tumor mAb treatment resulted in fast ADCP of tumor cells by Kupffer cells, which was dependent on FcgRI and FcgRVI. Uptake was independent of reactive oxygen (ROS) or nitrogen (RNS) species production, and followed by degradation, which prevented the development of liver metastases. Tumor cell capture and therapeutic efficacy was lost after depletion of Kupffer cells. As such, macrophages likely play an essential role in mAb‐mediated elimination of tumor cells. Therefore, by aiming to enhance macrophage recruitment and activity mAb therapeutical strategies of cancer patients may be optimized. Currently these strategies are investigated. Additionally, the role of macrophages in eliminating tumor cells in other tissues are studied. Support or Funding Information This project was financially supported by the Dutch Cancer Foundation (KWF) project VU2011–4931, and the Worldwide Cancer Research project 15‐1240.