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IFN-Gamma-Mediated Immunoevasive Strategies in Multiple Myeloma

Ciarlariello, Paul David
http://rave.ohiolink.edu/etdc/view?acc_num=osu1460656019

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
Natural killer (NK) cells are a major source of interferon-γ (IFN-γ) and may play a key role in innate immunity against multiple myeloma (MM). IFN-γ abrogates MM tumor cell in vitro proliferation, however, clinical trials of recombinant IFN-γ in patients with MM showed no benefit. MM cells exhibit strategies designed to evade NK cell surveillance and lysis. Herein, we provide evidence of a novel means of MM immune evasion in which IFN-γ appears to play a reciprocal relationship between MM and NK cells. Patients with MM exhibit higher levels of serum IFN-γ levels than in the healthy setting. NK cells produce IFN-γ in response to MM cells which express functional IFN-γ receptors. Stimulation with IFN-γ leads to increased transcription and expression of the inhibitory ligands HLA-E and PD-L1 by MM cells. This effect may be overcome by interruption of the NKG2A / HLA-E interaction. Intriguingly, MM cells release extracellular vesicles (EV) which are capable of enhancing IFN-γ production of NK cell, thus describing a potential cyclic mechanism of perpetual immune detriment. Taken in total, these results suggest that MM cells subvert the favorable effects of IFN-γ to attenuate NK cell tumor-directed cytotoxicity.
Natarajan Muthusamy (Advisor)
Don Benson, Jr. (Advisor)
Michael Caligiuri (Committee Member)
Gregory Lesinski (Committee Member)
Flavia Pichiorri (Committee Member)
126 p.
Immunology; Molecular Biology; Oncology
Interferon, Multiple Myeloma, Natural Killer Cell, immune evasion, immunoevasive, HLA-E, PD-L1, Major Histocompatibility Complex ,MHC, Human Leukocyte Antigen, HLA, inhibitory receptors, extracellular vesicles, microvesicles, exosomes

Recommended Citations

Citations

  • Ciarlariello, P. D. (2016). IFN-Gamma-Mediated Immunoevasive Strategies in Multiple Myeloma [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1460656019

    APA Style (7th edition)

  • Ciarlariello, Paul. IFN-Gamma-Mediated Immunoevasive Strategies in Multiple Myeloma. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1460656019.

    MLA Style (8th edition)

  • Ciarlariello, Paul. "IFN-Gamma-Mediated Immunoevasive Strategies in Multiple Myeloma." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1460656019

    Chicago Manual of Style (17th edition)

osu1460656019
696
© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.