Intestinal epithelial GSK3β governs fumarate-dependent neutrophil reprogramming to promote colorectal cancer.

Intestinal epithelial GSK3β regulates fumarate-dependent neutrophil reprogramming that promotes colorectal cancer progression.

• Why it matters: Understanding how tumor-infiltrating neutrophils (TINs) are reprogrammed is crucial because they contribute to tumor growth and resistance to therapy, yet their mechanisms remain unclear.
• What they did: Using mouse models and multiomics profiling, the study shows that GSK3β in intestinal epithelium influences fumarate accumulation, leading to epigenetic changes in TINs and promoting immunosuppressive neutrophil polarization.
• The result: Pharmacological inhibition of GSK3β with tideglusib reduces TIN reprogramming and enhances checkpoint blockade efficacy, suggesting potential for combined immunotherapies in colorectal cancer.