Healthcare (Commonwealth Union) – A recent investigation led by scientists at Keck Medicine of USC has identified a potentially powerful treatment combination for glioblastoma—a type of aggressive brain tumor with limited effective therapies.
The findings give an indication that integrating Tumor Treating Fields (TTFields) therapy—which sends specific targeted electric fields to the tumor site—with both immunotherapy (specifically pembrolizumab) and chemotherapy (temozolomide) can assist in the extension of patient survival.
The TTFields therapy functions by the application of low-intensity, alternating electric fields that interfere with the structures within cancer cells, blocking their division and spreading. This interference of cell division may assist in slowing tumor progression, providing patients an increased possibility of responding to treatment. The therapy is administered via mesh-like electrodes placed on the scalp, transfering the electric fields at carefully calibrated frequencies for roughly 18 hours each day.
The researchers also found that TTFields therapy boosts the presence of tumor-attacking T cells—immune cells responsible for recognizing and destroying cancer. When TTFields are used first, they appear to prime the immune environment, making subsequent immunotherapy more effective. These activated T cells not only persist longer but are also succeeded by stronger immune cells capable of targeting the tumor even more effectively.
“By using TTFields with immunotherapy, we prime the body to mount an attack on the cancer, which enables the immunotherapy to have a meaningful effect in ways that it could not before,” explained David Tran, MD, PhD, who is the chief of neuro-oncology with Keck Medicine, co-director of the USC Brain Tumor Center and corresponding author of the study. “Our findings suggest that TTFields may be the key to unlocking the value of immunotherapy in treating glioblastoma.”
TTFields are frequently used alongside chemotherapy in cancer care. Yet, despite this aggressive approach, outcomes for glioblastoma patients have historically remained grim. While immunotherapy has demonstrated promise in treating several other cancers, it has not yielded any important results against glioblastoma when administered alone.
When compared, this study found that combining immunotherapy with TTFields and chemotherapy led to 70% better results in overall survival rates. Interestingly, patients with bigger, inoperable tumors responded even more strongly to TTFields and experienced extended survival. This suggests that bigger tumors might actually enhance the immune response, potentially by offering more cancerous cells for the therapy to target and engage the body’s defenses.
Pembrolizumab, the immunotherapy used in this research, is classified as an immune checkpoint inhibitor (ICI). It fucntions by enhancing the immune system’s natural cancer-fighting capabilities—specifically by enhancing the performance of T cells, enabling them to better detect and destroy cancerous cells.
However, glioblastomas typically contain very few T cells. This is because they develop in the brain, which is protected by the blood-brain barrier—a selective shield that controls what can pass from the bloodstream into brain tissue. Unfortunately, this barrier can also prevent helpful immune cells and cancer treatments from reaching the tumor.
The immune-suppressive environment created by the blood-brain barrier is one of the main reasons therapies like pembrolizumab and chemotherapy often fail to produce meaningful results against glioblastoma. To overcome this, Dr. Tran proposed initiating an immune response from within the tumor itself—a strategy called in situ immunization—by using Tumor Treating Fields (TTFields).
The results of this study show that TTFields elicit a robust immune response inside the tumor when used in conjunction with immunotherapy. The body’s capacity to combat cancer from within is strengthened by checkpoint inhibitors like pembrolizumab, which further intensify the response due to this localized immune system activation.
Tran, who is also affiliated with the USC Norris Comprehensive Cancer Center described it like a team sport — immunotherapy brings in the attackers to go after the tumor, while TTFields work to break down the tumor’s defenses, and just like in sports, having a strong offense can be the most effective form of defense.
