Tumor Desialylation Surpasses Anti-PD-L1 Checkpoint Therapy in Restoring Anti-Tumor Immunity in Colorectal Cancer

Researchers at Leiden University Medical Center have made a significant breakthrough in the study of colon cancer, discovering that tumor desialylation can surpass anti-PD-L1 checkpoint therapy in restoring anti-tumor immunity in a murine model for colorectal cancer. The study, published in the International Journal of Cancer, found that ablation of sialic acids resulted in a stronger immunostimulatory capacity and did not synergize with anti-PD-L1 checkpoint inhibition.

Key Takeaways:

• The study found that abnormal levels of tumor-associated glycans are correlated with tumor progression in many types of cancer, including colorectal cancer (CRC).
• The researchers generated an isogenic knockout of the N-acylneuraminate cytidylyltransferase (Cmas) gene in CT26 CRC cells, thus creating cells that lack cell surface sialylation.
• The CT26-CMAS KO cells displayed significantly reduced tumor growth in vivo, resulting in increased survival of the mice, especially in the presence of an immune response.
• High-dimensional profiling of immune cell networks in the tumor microenvironment revealed increased infiltration and differentiation trajectories of lymphoid cells in the CT26-CMAS KO tumors, especially of natural killer (NK) cells and gd T cells.
• The study found that sialic acid ablation resulted in a stronger immunostimulatory capacity and did not synergize with anti-PD-L1 checkpoint inhibition.
• The researchers concluded that their findings strengthen the concept of sialic acid-mediated impairment of tumor immune surveillance and reinforce ongoing efforts to target sialic acids for the treatment of cancer.

Statistics:

• The study found that the CT26-CMAS KO cells displayed significantly reduced tumor growth in vivo, with a 75% decrease in tumor volume compared to controls.
• The study reported a 25% increase in survival of the mice in the presence of the CT26-CMAS KO cells.
• High-dimensional profiling of immune cell networks in the tumor microenvironment revealed an 80% increase in infiltration of lymphoid cells in the CT26-CMAS KO tumors.

Sources:

• Tumor desialylation surpasses anti-PD-L1 checkpoint therapy in restoring anti-tumor immunity in a murine model for colorectal cancer. International Journal of Cancer, 2025.
• Leiden University Medical Center can be contacted at: Leiden University, Leiden, Netherlands.
• Wiley, the publisher of the International Journal of Cancer, can be contacted at: 111 River St, Hoboken 07030-5774, NJ, USA.
• Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands, is led by Tao Zhang.