Sialylation profile and Siglec-E expression across tissues in the B16OVA melanoma mouse model.

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.