What protects cancer cells from the body’s immune system now will help fight against it – here’s how

The immune evasion abilities of cancer cells can be enhanced by developing a thicker glycocalyx barrier, according to recent research. The glycocalyx is a surface barrier that cancer cells form to evade the immune system. Researchers have studied the material properties of this barrier in great detail and uncovered information that could lead to better cell-based cancer immunotherapies.

Cancer cells use cell-surface mucins to create a glycocalyx that protects them from attack by immune cells. However, little is known about the physical properties of this barrier, particularly in the context of cell-based cancer immunotherapies. These therapies involve removing immune cells from a patient, modifying them to detect and destroy cancer cells, and then returning them to 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,” explains 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.”

According to Park, their laboratory has made significant progress in utilizing a technique known as scanning angle interference microscopy (SAIM) to measure the nanoscale dimensions of the glycocalyx in cancer cells. This imaging technique enables them to gain insights into the structural interconnection between cancer-associated mucins and the physical characteristics of the glycocalyx.

To replicate the glycocalyx in cancer cells, the researchers developed a cellular model that allowed them to accurately regulate the expression of cell-surface mucin. Using genetic techniques in conjunction with SAIM, they investigated the impact of cancer-associated mucins on the thickness of the glycocalyx at a nanoscale level, specifically looking at how the surface density, glycosylation, and crosslinking of these molecules affected the barrier’s thickness. They also examined how the thickness of the glycocalyx influenced a cell’s resistance to attacks from immune cells.

The findings of the study revealed that the thickness of the glycocalyx in cancer cells plays a significant role in immune evasion, and thinner glycocalyx barriers were more favorable for engineered immune cells to target cancer cells effectively.

Having gained this understanding, the researchers proceeded to engineer immune cells that feature specialized enzymes on their surface, enabling them to interact with and bind to the glycocalyx. Tests conducted at the cellular level confirmed that these immune cells could successfully penetrate the glycocalyx armor of cancer cells.

The next step for the researchers is to establish whether these results can be replicated in laboratory settings and, ultimately, in clinical trials.

At the annual meeting of the American Society for Biochemistry and Molecular Biology, Discover BMB, taking place in Seattle from March 25-28, Park will share the results of the study.

Image Credit: Getty & Sangwoo Park, Cornell University