Tumor-treating fields increase cytotoxic degranulation of natural killer cells against cancer cells

Tumor-treating fields (TTFs) are a non-invasive treatment for glioblastoma (GBM) that applies low-intensity, intermediate-frequency, alternating electric fields. Given a 5-year survival of less than 7% for GBM patients, multi-modal treatments are required to improve survival. Natural killer (NK) cells are innate lymphocytes that kill cancer cells and are thus a major target for new immunotherapy approaches. There is potential to combine TTFs with an NK cell-based therapy for GBM treatment. Here, we investigate the impact of TTFs on NK cell viability and functions. Exposure to TTFs does not affect NK cell viability or interferon (IFN)-γ production, a key NK cell function. Of significance, exposure to TTFs increases NK cell degranulation, a proxy of cell killing. These data suggest that the combination of TTFs and NK cell-based therapy may boost tumor cell killing. This provides a basis to further explore this combination, with the end goal of enhancing NK cell immunotherapy potential for patients with GBM. [Display omitted] •Tumor-treating fields (TTFs) do not affect natural killer (NK) cell viability•TTF exposure increased NK cell cytotoxic degranulation against GBM cells•TTFs had no effect on NK cell cytokine production Mylod et al. show that exposure of innate cytotoxic lymphocytes called natural killer cells to low-intensity, intermediate-frequency, alternating electrical fields for 18 h, termed “tumor-treating fields,” increases the killing of TMZ-sensitive and -resistant glioblastoma tumor cells.