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Cancer uses sugar residue to escape immune cells

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Newswise – A team of chemistry researchers from South Dakota State University have discovered how cancer cells use a simple residue of sugar to disguise themselves from the immune system. What they have learned will help scientists develop more effective cancer treatments.

“We used the prism of organic chemistry to understand how cancer cells escape the immune system,” explained Rachel Willand-Charnley, assistant professor of chemistry and biochemistry. The project is part of his research program in chemical biology, which uses various areas of chemistry to solve biological problems. Willand-Charnley’s research has applications in biotechnology and biomedicine.

Willand-Charnley, PhD students Mathias Anim and Albert Armoo, and Susan Grabenstein Roh, a biochemistry major who graduated with her bachelor’s degree in May, analyzed what is known as the sialic acid-Siglec receptor pathway. They examined the pathway in colon and lung cancer cells using cell lines modified with the CRISPR-Cas9 gene to determine how cancer cells escape detection by using sugars on their cell surface.

The findings are published in the June issue of Glycobiology, a peer-reviewed Oxford university research journal.. Roh, who at the time was a biochemistry student, is the first shared author of the article.. The project was supported by seed funding from the Willand-Charnley lab for new faculty members.

Willand-Charnley came to SDSU in 2018 after completing postdoctoral research under the tutelage of renowned chemistry professor Carolyn Bertozzi at the University of California at Berkeley and then Stanford University. His research combines expertise in organic chemistry, glycobiology and cancer immunology.

Using a sugar coating

“The cells are literally decorated with sugar residue called glycans. Cancers also have a sugar coating, ”said Willand Charnley. “How do sugars, like sialic acid, allow cancers to participate in an ‘immune breakout’? The immune system is programmed to identify cellular abnormalities, including deviations in the sugar layer, and mark them for degradation, but the question is, why are some cancer cells not killed by the immune system?

The article focuses on how cancers use simple residues of sugar, which she described as a sweet costume, to mimic healthy cells, thereby eluding the immune system. “This research will allow scientists to create better treatments that separate sugars, essentially removing the sugars from cancer cells,” said Willand-Charnley. “This will pave the way for more targeted and effective cancer therapies related to glycans. “

The two doctoral students see the advantages of this unique approach to improve cancer therapy. “It was really intriguing to realize that just one genetic modification could actually make cancers resistant to immunotherapy, making them invisible to the immune system,” said Anim, from Ashiaman, Ghana. He obtained his BA and MA in Biochemistry from Kwame Nkrumah University of Science and Technology in Kumasi Ashanti, Ghana.

Armoo, from Tema, Ghana, said: “For me it was interesting to find out that a sugar coating plays a role in resistance to chemotherapy. It is not always a drug metabolite, but also the patient’s own immune system capable of identifying cancer cells. He started a PhD at SDSU after earning his undergraduate degree from the University of Bradford in the UK and an MA from the Institute of Cancer Therapeutics at the University of Bradford.

Inspiring future scientists

Roh, from Mitchell, South Dakota, started working on the project in second grade. “I wanted to work with genetics, so when Dr Willand-Charnley talked about cell lines with knockout genes on the first day of my organic chemistry class, it piqued my interest in doing research with his group,” Roh said. “I was the first person to sign (to the project). “

Willand-Charnley said: “Undergraduates (in my lab) are treated like graduate students. I expect them to conduct their research like a graduate student.

Roh continued, “I found my own articles on the subject, read them, and explained why I felt they were relevant and what I learned from them (in weekly group meetings).” Every three weeks it was her turn to present her findings to the group in a professional manner. In 2019, Roh received the American Chemical Society Award for Best Undergraduate Research Poster.

Even though Roh was the only undergraduate student working on the project, she said, “I had a lot of responsibilities. I was able to be shared as the first author on paper because I put in an equal amount of work, which is what it took.

In addition to doing research part-time during the school year, she also spent two summers working full-time on the project. Roh, who is now a graduate research assistant in the Department of Biology and Microbiology, feels ready for graduate school, thanks to her experiments in Willand-Charnley’s lab.

In addition to leading successful research programs, Willand-Charnley also focuses on diversity and awareness. “One of my goals as a scientist is to increase diversity in STEM science,” said Willand-Charnley. However, “as students move through academia and get older we tend to have less diversity, why? One school of thought is that STEM science is seen as intimidating. So how can we solve this problem? “

Willand-Charley is working to launch an awareness program for K-5 students. “I want to spark interest in STEM science from an early age. What better way to generate interest and show science is fun than hands-on demonstrations with scientists in the classroom? “