The study explores how the glycocalyx, a protective layer on cancer cells, can be manipulated to enhance the effectiveness of immune cell therapies. The authors use a combination of techniques, including scanning angle interference microscopy (SAIM) and genetic engineering, to investigate the physical and biochemical properties of the glycocalyx. They find that the thickness of the glycocalyx is a critical factor in determining the susceptibility of cancer cells to immune cell attack. By engineering immune cells to express chimeric antigen receptors (CARs) or surface-displayed mucinases, they demonstrate that these enzymes can overcome the protective barrier provided by the glycocalyx, leading to improved cytotoxicity against cancer cells. The results suggest that immunoengineering strategies targeting the glycocalyx could enhance the efficacy of cancer immunotherapy.The study explores how the glycocalyx, a protective layer on cancer cells, can be manipulated to enhance the effectiveness of immune cell therapies. The authors use a combination of techniques, including scanning angle interference microscopy (SAIM) and genetic engineering, to investigate the physical and biochemical properties of the glycocalyx. They find that the thickness of the glycocalyx is a critical factor in determining the susceptibility of cancer cells to immune cell attack. By engineering immune cells to express chimeric antigen receptors (CARs) or surface-displayed mucinases, they demonstrate that these enzymes can overcome the protective barrier provided by the glycocalyx, leading to improved cytotoxicity against cancer cells. The results suggest that immunoengineering strategies targeting the glycocalyx could enhance the efficacy of cancer immunotherapy.