Description

Sialic Acid receptors and Langerin on Langerhans cells in a human skin model for vaccination strategies against melanoma

J. Lübbers, S. Duinkerken, R.J.E. Li, J.J. Garcia-Vallejo, Y. van Kooyk

Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands

Recent vaccination studies against melanoma use targeting the dendritic cells (DCs) or Langerhans cells (LC) in human skin to improve the induction of tumor specific CD4 and CD8 T cells. Targeting tumor specific proteins (Mart-1/gp100) bound to matrixes or dendrimers can be achieved by specific glycans that bind the C-type lectin receptors DC-SIGN and Langerin on DC or LC that improve cell specific targeting and to enhance cross-presentation¹. Tumor specific proteins could potentially also bind to other receptors like the sialic acid binding immunoglobulin type lectins (Siglecs), which are known for their immune-inhibitory function. Therefore, we study the presence of Siglecs on human skin resident LC with different immune status.

In a public available micro array data set² on epidermal LC and myeloid DC (mDC), data analysis on LC show an average expression of Siglec 3 and a similar expression of Siglec 10 compared to the mDC. Flowcytometry analysis on LC and CD1A⁺ dermal DC (dDC) derived from human skin, revealed a positive Siglec 10 expression. Future flowcytometry assays with other anti-Siglec antibodies will reveal the expression of Siglecs on human skin derived LC. Binding assays with glycan-tumor-dendrimers will reveal whether Siglecs on LC have an inhibitory function on the vaccination strategies developed against melanoma. Furthermore, studying the interaction of glycan tumor-dendrimers to the Siglecs and Langerin will reveal more insight in the pathways that are stimulated in the LC, aimed to further improve vaccination strategies for cancer immunotherapy.

References:

1. Joshi MD, Unger WJ, Storm G, Van Kooyk Y, Mastrobattista E. Targeting tumor antigens to dendritic cells using particulate carriers. J. Control. Release. 2012;161(1):25–37.

2. Hutter C, Kauer M, Simonitsch-Klupp I, et al. Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells. Blood. 2012;120(26):5199–5208.

Funding:

European research council grant: ERC-2013-AdG-339977