Tumor-Treating Fields Boost Natural Killer Cell Cytotoxicity in Glioblastoma

Researchers discover that tumor-treating fields (TTFs) increase cytotoxic degranulation of natural killer (NK) cells to eliminate malignant cells in patients with glioblastoma (GBM). Their findings, published in Cell Reports Physical Science, indicate that electric currents may promote NK cell cytotoxicity, supporting the potential of combining TTFs with NK cell-based immunotherapies to improve therapy response rates in patients.

These findings indicate that using TTF to enhance NK cells may represent a promising strategy for improving efficacy of immunotherapy treatments in GBM. Image Credit: © AkuAku - stock.adobe.com

GBM is an aggressive, incurable type of brain tumor that originates from glial cells in the brain or spinal cord, which rapidly spreads to surrounding healthy tissues in the brain. Although it’s a relatively common type of brain tumor, patients with GBM have poor survival rates with only 25% of patients surviving more than 1 year. Standard of care treatment typically involves surgery followed by chemotherapy and radiotherapy with the goal of slowing the progression of disease. However, patients often relapse and need advanced approaches to treatment.^1,2

According to prior studies, the GBM tumor microenvironment is understood to be immunosuppressive toward NK cells, which are cytotoxic toward various target cells, including tumor cells. This paved the way for the development of NK cell-based immunotherapy and advanced therapeutic options for patients with GBM.³

Another available therapy is TTF, which is administered through a portable TTF device that was approved by the FDA in 2011. The device features small transducers that are adhered to a shaved head and emit low- to intermediate- intensity electric fields through the skin to interrupt cancer cell division. The transducers are plugged into a small battery pack that can be easily carried and allows patients to receive treatment while continuing daily activities.

The researchers from the UK and Ireland identified that TTF enhanced the cytotoxic capabilities of NK cells, implying potential applications of a combined treatment approach including TTF and NK cell-based immunotherapy.^3,4

Using cell isolation and culture, degranulation assays, cell staining, and electrical field setup, the researchers were able to determine the impact of TTFs on NK cell viability and functions in peripheral blood samples. They found exposure to TTFs at a frequency of 200 kHz significantly enhanced degranulation of NK cells, indicating improved capabilities in destroying cancer cells. Further, TTFs did not compromise the viability of NK or the production of cytokines. These findings indicate that using TTF to enhance NK cells may represent a promising strategy for improving efficacy of immunotherapy treatments in GBM.⁴

“Little is known about whether TTFs can be used successfully in combination with immunotherapies, or even if TTFs might stop immunotherapy from working completely, said Clair Gardiner, professor at Trinity College Dublin School of Biochemistry and Immunology, in a press release. “The findings here, however, are very promising as our work shows that they had minimal negative impact on the NK cells and seemed to make them even more effective as killers.”⁵

The researchers plan to perform more in-depth studies investigating the potential and benefit of TTFs and NK cell-based therapy as a novel multifaceted approach to treatment of patients with GBM, leading to more targeted treatments and better patient outcomes.

REFERENCES

1. Glioblastoma. Mayo Clinic. June 20, 2024. Accessed August 5, 2024. https://www.mayoclinic.org/diseases-conditions/glioblastoma/symptoms-causes/syc-20569077#:~:text=Glioblastoma%20is%20a%20type%20of%20cancer%20that%20starts%20as%20a,more%20often%20in%20older%20adults
2. Glioblastoma prognosis. The Brain Tumour Charity. Accessed August 5, 2024. https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma-prognosis/
3. Mylod E, Conlon G, Jenkins E, et al. Tumor-treating fields increase cytotoxic degranulation of natural killer cells against cancer cells. Cell Rep. July 25, 2024. Accessed August 5, 2024. doi:10.1016/j.xcrp.2024.102119
4. TT fields (tumor treating fields) for brain tumors. John Hopkins Medicine. Accessed August 5, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/brain-tumor/tt-fields-tumortreating-fields-for-brain-tumors
5. Electrical currents may make body’s cancer-killing cells even better killers. News Release. July 25, 2024. Accessed August 5, 2024. https://www.eurekalert.org/news-releases/1052625