How cancer silences the immune system
In many cancers, the immune system is suppressed by cells within the tumor microenvironment, particularly tumor-associated macrophages (TAMs). Instead of attacking the tumor, these immune cells are recruited to support tumor growth, invasion, and metastasis. The research team will study Siglec-15, a receptor on TAMs that functions as a “master regulator” of their immune-suppressive activity. Siglec-15 is activated by glycans, complex sugar structures displayed on the surface of cancer cells. High levels of Siglec-15 are associated with tumor progression and poor outcomes in solid tumors such as lung, colorectal, and thyroid cancer. Because Siglec-15 and TAMs are often present in tumors that do not respond well to existing immunotherapies, it may serve as a valuable alternative target for treating these cancers.
Searching for the ‘sugar code’
Despite its potential, little is known about the specific sugar molecules that activate Siglec-15 or how this signaling affects immune cell behavior. By identifying these glycan ligands and unraveling the downstream effects of Siglec-15 activation, the research team aims to pave the way for new immunotherapies that reprogram TAMs and restore the immune system’s ability to attack cancer. "This project allows us to gain fundamental insights into how the immune checkpoint Siglec-15 works and may inspire the design of novel cancer therapies in the long-term", Büll says.
Biomolecular Chemistry
In 2022, Büll started his own research group at the Biomolecular Chemistry department, focusing on unraveling the mechanisms of cellular glycosylation and biological interactions with glycans. Büll currently studies the complex biosynthesis of glycans in the intestine and aims to apply this knowledge to glycoengineer human cells to produce glycoproteins with custom glycan structures. These kind of molecules can be applied to modulate the intestinal immune system and the intestinal microbiome. The department of Biomolecular Chemistry focuses on understanding autoimmune diseases like rheumatoid arthritis and Sjögren’s syndrome, emphasizing the role of B cells and the impact of post-translational modifications such as glycosylation on immunological self-tolerance. The research group is part of IMM.
KWF
Every person in the Netherlands will at some stage have an experience with cancer. When you have cancer, it disrupts your life, but also when someone you know has the disease. The consequences are overwhelming. To all those millions of lives, every day KWF Dutch Cancer Society makes a difference for more than 75 years. We not only fight this disease, but we also strive for a better life living with cancer.
Alpe d'HuZes
Alpe d'HuZes is a unique sporting event where as much money as possible is raised for cancer research and for improving the quality of life of people with cancer. On a single day, 5000 participants will bike, hike or run the Alpe d'Huez. Attempting a maximum of six climbs, under the motto 'giving up is not an option'. Since 2006, we have raised more than 226 million euros.