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Updated: Jul 3, 2025

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Immunoengineering can overcome the glycocalyx armour of cancer cells
Sangwoo Park1,2, Marshall J Colville1,2, Justin H Paek3
1Field of Biophysics, Cornell University, Ithaca, NY, USA.
Abstract:
Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Changes in glycocalyx thickness of approximately 10 nm can alter the susceptibility to immune cell attack. Enhanced stimulation of natural killer and T cells through equipment with chimeric antigen receptors can improve the cytotoxicity against mucin-bearing target cells. Alternatively, cytotoxicity can be enhanced through engineering effector cells to display glycocalyx-editing enzymes, including mucinases and sialidases. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells.
Insights
Cancer cells shield themselves from immune attack using their glycocalyx. Reducing glycocalyx thickness or engineering immune cells can enhance natural killer cell-mediated cytotoxicity against cancer.
Area of Science:
- Cancer Biology
- Immunology
- Biophysics
Background:
- The cancer cell glycocalyx acts as a barrier against immune surveillance.
- Understanding the molecular regulation of glycocalyx physical properties is crucial for overcoming immune evasion.
Purpose of the Study:
- To investigate how cancer-associated mucins and their glycosylation influence glycocalyx thickness.
- To determine the impact of glycocalyx thickness on immune cell interactions and cytotoxicity.
- To explore immunoengineering strategies to enhance anti-cancer immunity.
Main Methods:
- Analysis of cancer-associated mucins and their glycosylation.
- Measurement of glycocalyx nanoscale material thickness.
- Assays for natural killer cell-mediated cytotoxicity.
- Engineering of effector cells with chimeric antigen receptors and glycocalyx-editing enzymes.
Main Results:
- Cancer-associated mucins and their glycosylation determine glycocalyx thickness.
- Natural killer cell-mediated cytotoxicity is inversely correlated with glycocalyx thickness.
- A ~10 nm change in glycocalyx thickness significantly impacts susceptibility to immune attack.
- Enhanced stimulation of natural killer and T cells via chimeric antigen receptors improves cytotoxicity against mucin-expressing cells.
- Engineering effector cells with mucinases and sialidases enhances cytotoxicity.
Conclusions:
- The glycocalyx serves as a physical barrier contributing to cancer immune evasion.
- Immunoengineering strategies, including glycocalyx editing and enhanced immune cell stimulation, can overcome this barrier.
- Targeting the cancer cell glycocalyx offers a promising approach for cancer immunotherapy.
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