Research Highlights

Tumor vaccination: C-lectin a new receptor

Lungs of mice challenged with melanoma cells and treated (top) or untreated (bottom) with the fusion antibody and adjuvant. Image by courtesy of Dr David Sancho-Madrid, Immunobiology Laboratory, London Research Institute, Cancer Research UK.

The dendritic cell lectin receptor DC-SIGN (dendritic cell (DC)-specific intercellular adhesion molecule 3 grabbing nonintegrin) is involved in human immunodeficiency virus infection and has been used for attempts in cancer tumor therapy. Now, in the Journal of Clinical Investigation, Sancho et al. characterize a new DC lectin receptor with promising therapeutic potential.

Mouse CD8⁺ DCs, in contrast to CD8^- DCs, cross-present exogenous antigens on major histocompatibility complex class I molecules. Thus, tumor-derived antigens bound by CD8⁺ cells can elicit a strong cytolytic (CTL) T-cell response against the tumor. Screening gene expression data, the authors discovered a receptor discerning CD8⁺ from CD8^- cells termed DNGR-1 (DC, natural killer (NK) lectin group receptor-1) owing to its structural relatedness to receptors such as dectin-1, which occurs on NK cells. Flow cytometry indicated that DNGR-1 solely occurs on CD8⁺ cells, suggesting that it is a defining feature of them.

Sancho et al. noted that a fluorescence-labeled antibody against DNGR-1 was readily endocytosed into the DCs. This prompted them to fuse an anti-DNGR antibody with the immunodominant peptide of the chicken ovalbumin antigen. When the authors injected the fusion antibody and an adjuvant into mice, antigen-specific CTL T cells were expanded and activated, indicating a potential of DNGR-1 for tumor immunotherapy. Indeed, mice vaccinated with the same fusion-adjuvant combination developed much fewer metastases when challenged with melanoma cells expressing the ovalbumin antigen. Lastly, the authors — and researchers in an independent study — found that DNGR-1 is also expressed on human immune cells where it has a similar specificity for a subgroup of DCs.

The results of the presented study are remarkable in the characterization of a novel lectin receptor that defines a subset of DCs able to induce a CTL T-cell response. It will be interesting to know whether glycan ligands for DNGR-1 have the potential to increase the immune response.

Author: Mirko von Elstermann