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Full text release has been delayed at the author's request until December 14, 2026

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The Role of K+ Channels in Modulating NK Cell Functions in Head and Neck Cancer

Alshwimi, Abdulaziz
http://orcid.org/0000-0002-1070-7
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733399326651794

Abstract Details

2024, PhD, University of Cincinnati, Medicine: Molecular, Cellular and Biochemical Pharmacology.
CD8+ T-cells and natural killer (NK) cells are the primary lines of defense against tumor cells. However, the tumor microenvironment incapacitates the anti-tumor capabilities of these immune cells, including impairing the ability of T and NK cells to infiltrate the tumor. Our laboratory has shown that tumors influence T cells in part by manipulating the activity of KCa3.1 K+ channels that in turn regulate cytokine release, cytotoxicity, and chemotaxis of T-cells. However, less is known about the role(s) of K+ channels in NK cell antitumor functionality. Herein, we investigate the role of KCa3.1 channels in human NK cell functionality in the context of head and neck cancer. Selective blockade of KCa3.1 using TRAM-34 inhibited the ability of NK cells from both healthy donors and head and neck squamous cell carcinoma (HNSCC) patients to undergo chemotaxis. Correspondingly, pharmacological activation of KCa3.1 increased chemotactic responses of NK cells. Moreover, SKA-31, a selective KCa3.1 activator, enhanced anti-tumor immune responses in a humanized HNSCC mouse model generated by implantation of Cal27 cells (a human HNSCC cell line) and healthy donor peripheral blood mononuclear cells into immunodeficient mice. SKA-31 treatment resulted in a 7-fold increase in total NK cells and 23-fold increase in functionally active (granzyme B positive) NK cells into these tumors. These data highlight the critical role of KCa3.1 channels in anti-tumor immunity and open the possibility of targeting KCa3.1 to develop new immunotherapies in HNSCC.
Laura Conforti, Ph.D. (Committee Chair)
Katharine Hobbing (Committee Member)
Trisha Wise-Draper, M.D. Ph.D. (Committee Member)
Stephen Waggoner, Ph.D. (Committee Member)
Steven Kleene, Ph.D. (Committee Member)
150 p.
Pharmacology
; ion channels; Head and neck cancer; cancer immunology; NK cells; T cells

Recommended Citations

Citations

  • Alshwimi, A. (2024). The Role of K+ Channels in Modulating NK Cell Functions in Head and Neck Cancer [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733399326651794

    APA Style (7th edition)

  • Alshwimi, Abdulaziz. The Role of K+ Channels in Modulating NK Cell Functions in Head and Neck Cancer. 2024. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733399326651794.

    MLA Style (8th edition)

  • Alshwimi, Abdulaziz. "The Role of K+ Channels in Modulating NK Cell Functions in Head and Neck Cancer." Doctoral dissertation, University of Cincinnati, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733399326651794

    Chicago Manual of Style (17th edition)

ucin1733399326651794
© 2024, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.
Release 3.2.12