Scientists Find How High Blood Sugar Helps Cancer Cells Hide From the Immune System

Cancer cells can evade the immune system by surrounding themselves with a dense, sugar-derived coating called the glycocalyx that makes them harder for immune cells to recognize. Researchers at Sanford Burnham Prebys Medical Discovery Institute and collaborating institutions across North America have now identified the environmental conditions that help cancer cells build this protective layer, and a potential way to reduce it. The findings were published August 7 in Science Advances.

Lead author Kevin Tharp, an assistant professor in the Cancer Metabolism and Microenvironment Program at the Sanford Burnham Prebys NCI-Designated Cancer Center, had previously studied how physical pressure on cells changes their mitochondrial function, and hypothesized that the stiffness of primary tumors — which are typically stiffer than surrounding tissue — could help explain the metabolic changes seen in cancer. His team grew cells in stiff or soft environments, using either a standard laboratory growth medium or one designed to match the nutrient composition of the human body, under both normal and elevated glucose levels.

Excess glucose thickened the glycocalyx, but only in cells grown in the medium that mimicked the human body's actual nutrient composition. The researchers traced this effect to a protein called heat shock factor 1 (HSF1), previously linked to the progression and spread of breast cancer: hyperglycemia only helped cancer cells evade immune detection when HSF1 was present and the cells were grown in tumor-like conditions.

"Our findings indicate that changes in mitochondrial function lead to the synthesis of cell surface sugar-derived molecules that make it difficult for the immune system to recognize and kill cancer cells," said Tharp. "Now that we know this, this creates an enormous drug discovery opportunity to take away the surface coating that protects them from immune surveillance, and we think this will be a really effective strategy to attack metastatic disease and improve immunotherapy responses."