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Rapid and potent induction of cell death and loss of NK cell cytotoxicity against oral tumors by F(ab′)2 fragment of anti-CD16 antibody

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Abstract

Freshly isolated untreated NK cells undergo rapid apoptosis and lose their cytotoxic function upon the addition of F(ab′)2 fragment of anti-CD16 antibodies. Loss of NK cell cytotoxic function after treatment with F(ab′)2 fragment of anti-CD16 antibody can be seen against K562 and UCLA-2 oral tumor cells when either added immediately in the co-cultures of NK cells with the tumor cells or after pre-treatment of NK cells with the antibody before their addition to the tumor cells. Addition of Interleukin-2 (IL-2) in combination with anti-CD16 antibody to NK cells delayed the induction of DNA fragmentation in NK cells, and even though decreased cytotoxicity could still be observed against K562 and UCLA-2 oral tumors when compared to IL-2 alone treated NK cells, the cytotoxicity levels remained relatively higher and approached those obtained by untreated NK cells in the absence of antibody treatment. No increases in IFN-γ, Granzymes A and B, Perforin and TRAIL genes could be seen in NK cells treated with anti-CD16 antibody. Neither secretion of IFN-γ nor increased expression of CD69 activation antigen could be observed after the treatment of NK cells with anti-CD16 antibody. Furthermore, IL-2 mediated increase in CD69 surface antigens was down-modulated by anti-CD16 antibody. Finally, the addition of anti-CD16 antibody to co-cultures of NK cells with tumor target cells was not inhibitory for the secretion of VEGF by oral tumor cells, unlike those co-cultured with untreated or IL-2 treated NK cells. Thus, binding and triggering of CD16 receptor on NK cells may enhance oral tumor survival and growth by decreased ability of NK cells to suppress VEGF secretion or induce tumor cell death during the interaction of NK cells with oral tumor cells.

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Acknowledgment

This manuscript is dedicated to the memory of Frank Joseph Jewett for his courageous fight against cancer.

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Authors and Affiliations

  1. Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, The Jonsson Comprehensive Cancer Center (JCCC), Dental Research Institute, UCLA School of Dentistry, Los Angeles, CA, 90095, USA

    Anahid Jewett, Antonia Teruel & Marcela Romero

  2. Department of Head and Neck Surgery, UCLA School of Medicine, Los Angeles, CA, 90095, USA

    Christian Head

  3. Department of Radiation Oncology, UCLA School of Medicine, Los Angeles, CA, 90095, USA

    Nicholas Cacalano

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  1. Anahid Jewett
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  2. Antonia Teruel
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  3. Marcela Romero
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  4. Christian Head
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  5. Nicholas Cacalano
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Correspondence to Anahid Jewett.

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This work was supported by RO1-DE18830 from NIH.

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Jewett, A., Teruel, A., Romero, M. et al. Rapid and potent induction of cell death and loss of NK cell cytotoxicity against oral tumors by F(ab′)2 fragment of anti-CD16 antibody. Cancer Immunol Immunother 57, 1053–1066 (2008). https://doi.org/10.1007/s00262-007-0437-6

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