Scientists discover how cancer cells evade immune system
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Cancer cells are notoriously hard to tackle as they hide from the body’s immune system. One way they do this is by forming a thin surface barrier called the glycocalyx.
Now, a new study is exploring the material properties of this barrier with unprecedented resolution, revealing information that could significantly increase the efficiency of today's cell-based cancer immunotherapies.
This is according to a press release published Sunday by the American Society for Biochemistry and Molecular Biology.
The glycocalyx is developed with high levels of cell-surface mucins, which are thought to help protect the cancer cell from immune cell attack. However, up to now, there has been limited understanding of this barrier particularly as it relates to cell-based cancer immunotherapies.
These types of treatments involve removing immune cells from a patient, modifying them to seek and destroy cancer, and then putting them back into the patient’s body.
“We found that changes in the thickness of the barrier that were as small as 10 nanometers could affect the antitumor activity of our immune cells or the engineered cells used for immunotherapy,” said Sangwoo Park, a graduate student in Matthew Paszek’s Lab at Cornell University in Ithaca, New York.
“We used this information to engineer immune cells that can get through the glycocalyx, and we hope this approach could be used to enhance current cell-based immunotherapies.”
“Our lab has advanced a powerful strategy called scanning angle interference microscopy (SAIM) for measuring the nanoscale dimensions of the cancer cell glycocalyx,” said Park. “This imaging technique allows us to understand the structural relationship of cancer-associated mucins to the biophysical properties of the glycocalyx.”
Mimicking cancer cells
Through the introduction of a cellular model, the researchers were able to precisely control the cell-surface mucin expression to mimic the cancer cell glycocalyx. Next, they merged SAIM with genetic approaches to study how the surface density, glycosylation and crosslinking of cancer-associated mucins affect the thickness of the barrier at the nanoscale and how the glycocalyx thickness affected a cell’s resistance to attack by immune cells.
What they found was nothing short of impressive: the thickness of cancer cells' glycocalyx is one of the major parameters determining immune cell evasion and engineered immune cells work better if the glycocalyx is thinner.
As a result of these findings the researchers then engineered immune cells with special enzymes on their surface to allow them to attach to and interact with the glycocalyx. They then found that these specialized immune cells were able to overcome the glycocalyx armor of cancer cells, according to the study's statement.
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