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Updated: Jun 2, 2026
Generation of Monocyte-Derived Dendritic Cells with Differing Sialylated Phenotypes
Published on: October 20, 2023
Sialylation profile and Siglec-E expression across tissues in the B16OVA melanoma mouse model
Magali Coccimiglio1,2,3, Tao Zhang4, Katarzyna Olesek1,2,3
1Department of Molecular Cell Biology & Immunology, Amsterdam UMC Location VUmc, De Boelelaan 1108, 1081 HZ, 1007 MB, Amsterdam, The Netherlands.
Abstract:
Increased sialylation of tumour cells, which favours tumour growth and immune evasion, has been described using in vitro and in vivo models, leading to the first in-human clinical trial targeting sialylation in cancer. One important limitation is that the biology of sialic acids and their receptors (Siglecs), which have been considered as immune checkpoints, is different between mice and human. Hence, it is crucial to fully describe and investigate sialic acids and Siglecs expression in animal models, to define their advantages and limitations. Here, we determined the sialylation profile of the widely-used B16OVA melanoma mouse model using flow cytometry and glycomics. B16OVA cells express Siglec-E-binding sialoglycans, therefore we explored Siglec-E expression across various tissues from tumour-bearing mice. We identified that Siglec-E is expressed on myeloid cells and CD8+ T cells in the tumour microenvironment. However, in spleen, blood and tumour-draining lymph nodes not only CD8+ but also CD4+ T cells expressed Siglec-E. Interestingly, Siglec-E+ and Siglec-E- T cells presented distinct expression of PD-1 across tissues, suggesting different regulation mechanisms for the expression of these immune checkpoints. Our work provides an investigation of the sialoglycans on B16OVA cells and the expression of their receptor Siglec-E across tissues, which is of importance for future therapeutic studies targeting the sialic acids-Siglec axis, especially in combination with anti-PD-1 therapies.
Insights
This study investigated sialic acids and Siglec-E expression in a mouse melanoma model. Findings reveal Siglec-E
Area of Science:
- Immunology
- Glycobiology
- Cancer Research
Background:
- Increased sialylation of tumor cells promotes tumor growth and immune evasion.
- The sialic acid-Siglec axis acts as an immune checkpoint, but differences exist between mice and humans.
- Understanding mouse models is crucial for translating findings to human cancer therapies.
Purpose of the Study:
- To characterize the sialylation profile of B16OVA melanoma cells.
- To investigate the expression of Siglec-E, a sialic acid receptor, in various tissues of tumor-bearing mice.
- To explore the relationship between Siglec-E and PD-1 expression on T cells.
Main Methods:
- Flow cytometry and glycomics were used to determine the sialylation profile of B16OVA cells.
- Siglec-E expression was analyzed in different tissues from tumor-bearing mice.
- Expression of PD-1 on Siglec-E positive and negative T cells was examined.
Main Results:
- B16OVA cells express Siglec-E-binding sialoglycans.
- Siglec-E is expressed on myeloid cells and CD8+ T cells within the tumor microenvironment.
- In spleen, blood, and lymph nodes, both CD4+ and CD8+ T cells express Siglec-E, with distinct PD-1 expression patterns.
Conclusions:
- This study provides a detailed analysis of sialoglycans and Siglec-E expression in the B16OVA mouse model.
- Findings are important for future therapeutic strategies targeting the sialic acid-Siglec axis in cancer.
- The distinct expression of Siglec-E and PD-1 suggests complex regulation of immune checkpoints, relevant for combination therapies, particularly with anti-PD-1 treatments.
