Researchers have developed a method that utilizes ultrasound to alter the behavior of T cells, which are crucial in fighting cancer, by enhancing their ability to allow substances to pass through their membranes. They focused ultrasound beams on freshly isolated human immune cells along with clinically safe microbubbles that act as contrast agents. The ultrasound causes the microbubbles to vibrate at very high frequencies, creating a push-pull effect on the membranes of the T cells. This process simulates the natural reaction of T cells to antigens. As a result, the T cells begin to release essential signaling molecules that would typically be hindered by the unfavorable environment of the tumor. Importantly, this method does not harm the T cells.
A new study by a team of Concordia researchers from the Biology and Physics departments introduces an innovative technique to combat cancer tumors. This method employs ultrasound-guided microbubbles—a technology already commonly used in medical imaging and drug administration.
In an article published in the journal Frontiers in Immunology, the researchers outline a technique using ultrasound to enhance the activity of T cells that combat cancer by increasing their membrane permeability. They explored how this modification can affect the release of over 90 types of cytokines, which are vital signaling molecules for immune function.
The researchers focused ultrasound beams on human immune cells obtained fresh, using clinically-approved contrast microbubbles. When exposed to ultrasound, these microbubbles vibrate at high frequencies, exerting a push-pull effect on the T cell membranes. This simulates how T cells naturally react to antigens. Consequently, T cells start secreting crucial signaling molecules that are otherwise limited by the tumor’s inhospitable environment, without damaging the cells themselves.
“We are integrating ultrasound and microbubbles to influence brain immunology within the innovative field of cancer immunotherapy, which seeks to utilize our immune cells to combat cancer,” states Brandon Helfield, an associate professor of biology and physics as well as the supervising author of the paper.
Reactivating Cells
This innovative approach directly addresses a significant obstacle in the body’s natural cancer response: tumors’ ability to suppress T cells from producing cytokines and other vital proteins once they infiltrate the tumor itself.
“The microbubbles can effectively reactivate the cells that have been silenced within the tumor,” explains Ana Baez, the lead author and PhD candidate. “This process assists in releasing the necessary proteins for promoting additional immune and blood cell growth, creating a beneficial feedback mechanism.”
The researchers discovered that the changes in cytokine release were dependent on time, showing an increase in cytokines by a factor of 0.1 to 3.6 times compared to untreated cells over 48 hours. Moreover, they observed that increased cell membrane permeability due to ultrasound generally led to a decrease in the quantity of cytokines released.
Although the findings are still in preliminary stages from benchtop experiments, the authors are optimistic that this study will enhance their understanding of the various pathways through which the immune system can combat cancer. They also believe that this research direction could improve and enhance current cancer therapies and cellular treatments.
“Microbubbles are already in clinical use as imaging tools,” Helfield notes, who holds the Tier II Canada Research Chair in Molecular Biophysics in Human Health. “In the future, we might adjust the ultrasound beam from imaging to a therapeutic application. This would allow us to target T cells specifically where the beam is focused.”
“We might also be able to incorporate cancer-targeting drugs into this treatment,” Baez adds. “Moreover, this technique is entirely non-invasive, allowing us to repeat the process as needed.”
Davindra Singh, Stephanie He, Mehri Hajiaghayi, Fatemeh Gholizadeh, and Peter Darlington contributed to this study.
This research received support from the Canada Research Chairs Program, the Cancer Research Society, and the Canadian Institutes of Health Research (CIHR).
