Tumor associated glycoproteins are a group of antigens with high immunogenic interest: the glycoforms generated by the aberrant glycosylation are tumor specific and the novel glycoepitopes exposed can be targets of tumor specific immune responses. The MUC1 antigen is one of the most relevant tumor associated glycoprotein. In cancer, MUC1 loses polarity, becomes overexpressed and hypoglycosylated. Changes in glycan moieties contribute to MUC1 immunogenicity and can modify the interactions of tumor cells with antigen presenting cells such as dendritic cells (DCs) with an impact on the overall anti-tumor immune response. Here we show that also the form of the MUC1 antigen i.e. soluble or as microvesicles cargo influences MUC1 processing in DCs. In fact, MUC1 carried by microvesicles translocates from endolysosomal/HLAII to HLAI compartment and is presented by DCs to MUC1 specific CD8+ T cells stimulating IFNγ responses, while the soluble MUC1 is retained in the endolysosomal/HLAII compartment independently by the glycan moieties and by the modality of internalization (mediated or not by receptors). Also, MUC1 translocation to HLAI compartment is accompanied by deglycosylation that generates novel MUC1 glycoepitopes. Transfer of tumor associated glycoproteins to DCs mediated by microvesicles may be a relevant biological mechanism in vivo contributing to define the type of immunogenicity elicited. Furthermore, these results have important implications for the design of glycoprotein-based immunogens for cancer immunotherapy.
- Received August 6, 2013.
- Revision received October 14, 2013.
- Accepted October 22, 2013.
- Copyright © 2013, American Association for Cancer Research.