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Updated: May 24, 2026
Generation of Monocyte-Derived Dendritic Cells with Differing Sialylated Phenotypes
Published on: October 20, 2023
Tumor sialylation regulates G-CSF stability and promotes neutrophil-mediated immunosuppression in breast cancer
Stefan Mereiter1,2, Gustav Jonsson3,4,5, Tiago Oliveira3,4
1Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria. stefan.mereiter@meduniwien.ac.at.
Abstract:
Breast cancer is the most prevalent cancer among women, yet immune checkpoint inhibitors remain largely ineffective in the majority of patients. Here we show that tumor sialylation is negatively associated with T cell infiltration across molecular breast cancer subtypes. In preclinical models, both genetic and pharmacologic inhibition of tumor cell sialylation reshape the tumor microenvironment by reducing immunosuppressive neutrophil infiltration, while CD8⁺ effector and Tcf7⁺ memory T cells are increased within the mammary tumors. Mechanistically, sialylation enhances the serum half-life of granulocyte colony-stimulating factor (G-CSF), a key driver of neutrophilic immunosuppression, and dampens tumor cell immunogenicity by limiting MHC-I surface expression. Disruption of sialylation sensitizes resistant mammary tumors to CD8⁺ T cell-mediated killing and anti-PD-1 therapy in multiple breast cancer models. These findings establish tumor sialylation as a key mechanism of immune evasion and a potential therapeutic target in breast cancer.
Insights
Tumor sialylation hinders T cell infiltration in breast cancer. Inhibiting sialylation boosts anti-tumor immunity and enhances responses to immunotherapy, revealing a new therapeutic target.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Breast cancer affects many women, but immune checkpoint inhibitors (ICIs) have limited efficacy.
- Understanding mechanisms of immune evasion is crucial for improving breast cancer treatment.
Purpose of the Study:
- To investigate the role of tumor sialylation in breast cancer immune evasion.
- To explore sialylation as a potential therapeutic target to enhance anti-tumor immunity and ICI efficacy.
Main Methods:
- Analysis of tumor sialylation and T cell infiltration across breast cancer subtypes.
- Preclinical models using genetic and pharmacologic inhibition of tumor sialylation.
- Assessment of tumor microenvironment changes, including immune cell populations and MHC-I expression.
- Evaluation of tumor response to sialylation disruption combined with anti-PD-1 therapy.
Main Results:
- Tumor sialylation negatively correlates with T cell infiltration in breast cancer.
- Inhibition of sialylation reduced immunosuppressive neutrophils and increased CD8+ effector and memory T cells.
- Sialylation was found to prolong the half-life of G-CSF and decrease MHC-I expression on tumor cells.
- Disrupting sialylation sensitized resistant tumors to T cell-mediated killing and anti-PD-1 therapy.
Conclusions:
- Tumor sialylation is a significant mechanism of immune evasion in breast cancer.
- Targeting tumor sialylation can reprogram the tumor microenvironment to promote anti-tumor immunity.
- Sialylation inhibition represents a promising strategy to overcome resistance to immunotherapy in breast cancer.
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