Melanoma-derived extracellular vesicles bear the potential for the induction of antigen-specific tolerance

The suppression of anti-cancer immune responses by tumors is central to their survival. Cancer-induced immunosuppression is antigen-specific rather than systemic and the mechanisms for the antigen specificity are incompletely understood. In this publication, researchers from the Polish Academy of Sciences and the Medical University of Lodz provide evidence that melanoma-derived small extracellular vesicles (sEVs) – such as exosomes – are able to induce antigen-specific immunological tolerance. sEVs can transport functional MHC class I molecules with bound peptides derived from tumor-associated antigens (TAAs) a process that is called cross-dressing. These MHC-peptide complexes are taken up by antigen processing cells (APCs) and appear at the cell surface. The same sEVs that transport the MHC-TAA-peptide complexes may contain immunosuppressive cytokines and miRNAs to induce an immunosuppressive phenotype in the targeted APCs. Stimulation of a suppressive phenotype in the very same APCs that take up TAAs may yield antigen-specific tolerance. Tolerance induction was partly mediated by TGF-ß carried by sEVs. The presented results indicate the existence of a hitherto undescribed mechanism that offers an explanation for antigen-specific tolerance induction mediated by cancer-derived sEVs.