KCa3.1 channels regulate NK cell tumor infiltration in head and neck cancer

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B970
Abstract ID: 7625

Presenting Author:
Abdulaziz O Alshwimi , Graduate Student at Univ. of Cincinnati Col. of Med.

Abstract:

NK cells are important mediators of antitumor immunity in head and neck squamous cell carcinoma (HNSCC) where they need to infiltrate the tumor and make contact with the cancer cells in order to kill them. However, low NK cell tumor infiltration has been associated with poor outcomes and immunotherapy resistance. Previously we have shown that KCa3.1 channels are important regulators of Ca²⁺ fluxes and chemotaxis in T cells (Chimote et al., Science Signaling 2018). However, little is known about the role of KCa3.1 in NK cell chemotaxis. In vitro studies with human NK cells activated with IL2/IL15 showed that the KCa3.1 selective blocker TRAM-34 inhibited chemotaxis and random migration, while pharmacological KCa3.1 activation increased chemotaxis. In vivo experiments with a humanized HNSCC mouse model generated by implantation of Cal27 cells (a human HNSCC cell line) in immune-deficient NSG mice, followed by injection of healthy donor PBMCs, showed that SKA-31, a selective KCa3.1 activator, significantly reduced tumor burden compared to vehicle. This effect was not due to an effect of SKA-31 on cancer cells. HNSCC cell lines and patient tumor biopsies showed low to null KCa3.1 expression, and KCa3.1 activation did not increase their proliferation. However, quantitation of immunohistochemistry images of tumors from the HNSCC mice revealed a 2-fold increase in infiltrated NK cells in the SKA-31 treated group, thus supporting the important role of KCa3.1 in anti-tumor immunity.