One way cancer cells hide from the body’s immune system is by forming a thin surface barrier called the glycocalyx. In the new study, the researchers examined the material properties of this barrier with unprecedented resolution, uncovering information that could help improve current cellular cancer immunotherapies.
Cancer cells often form a glycocalyx with high levels of cell surface mucins, which are thought to help protect cancer cells from attack by immune cells. However, physical understanding of this barrier remains limited, especially with regard to cellular cancer immunotherapy, which involves removing immune cells from a patient, modifying them to seek out and destroy cancer, and then turning them back into the patient.
“We found that changes in barrier thickness as small as 10 nanometers affect the antitumor activity of our immune cells or immunotherapy engineered cells,” said Sangwu Park, a graduate student in the Matthew Paszek lab at Cornell University at ISAB, New York. “We have used this information to design immune cells that can pass through the glycocalyx, and we hope this approach can be used to improve modern cellular immunotherapy.” Biology.
“Our lab has come up with a powerful strategy called scanning angle interference microscopy (SAIM) to measure the nanosized glycocalyx of cancer cells,” said Park. “This imaging technique allowed us to understand the structural relationship of cancer-associated mucins with the biophysical properties of the glycocalyx.”
The researchers created a cellular model to precisely control the expression of cell surface mucins to mimic the glycocalyx of cancer cells. They then combined SAIM with a genetic approach to investigate how the surface density, glycosylation, and cross-linking of cancer-associated mucins affect nanoscale barrier thickness. They also analyzed how the thickness of the glycocalyx affects the resistance of cells to attack by immune cells.
The study shows that the thickness of the cancer cell glycocalyx is one of the main parameters that determine immune cell evasion, and that engineered immune cells work better if the glycocalyx is thinner.
Based on this knowledge, the researchers have designed immune cells with special enzymes on their surface that allow them to attach to and interact with the glycocalyx. Experiments at the cellular level have shown that these immune cells are able to overcome the glycocalyx armor of cancer cells.
The researchers then plan to determine whether these results can be replicated in the lab and eventually in clinical trials.
Sangwoo Park will present this study (summary) during the “Regulatory Glycosylation in the Spotlight” session on Sunday, March 26, 2-3 pm PT, Seattle Convention Center, room 608. Contact the media team for more information or free pass to the conference.
Nancy D. Lamontagne is a science writer and editor at Creative Science Writing in Chapel Hill, North Carolina.
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Post time: May-22-2023