Exosomes and immune surveillance of neoplastic lesions: a review

Abstract

The immune system has been reported to suppress the development and progression of neoplastic lesions; however, the exact mechanisms by which neoplastic lesions and the immune system interact are not well understood. Within the last decade, tiny membrane bound particles, approximately 30–100 nm in diameter, have been observed in the blood and other body fluids. These particles, currently called exosomes, are released from many types of tissues including tumors, and they contain and carry many proteins, and mRNAs and microRNA species. We review here how tumors suppress the immune system, especially by the formation of exosomes. Exosomes released from tumors are carried in part by the vascular system to distant cells, which phagocytose them. Depending on the proteins, mRNAs or microRNAs in the exosomes and the cell type, phagocytosis of exosomes may provide a modulating signal to the cell. In the case of exosomes from tumors, uptake of the exosomes by cells of the immune system has been reported to have three main effects: 1) suppression of the number and activity of natural killer cells, 2) suppression of the activity of T cells and 3) suppression of the number and maturation of mature dendritic cells.

Key words::

• cancer
• dendritic cells
• exosomes
• immune surveillance
• intraepithelial neoplasia
• NK cells
• PGE2
• T cells
• TGFβ
• TNFα

Acknowledgments

Supported in part by the grant for the Early Detection Reference Laboratory at UAB of the Early Detection Research Network 5U24CA086359-10 to WEG, National Institutes of Health grant numbers RO1CA116092, RO1CA107181, RO1AT004294, R01CA137037 to HGZ, Birmingham Veterans Administration Medical Center Merit Review Grants to HGZ, and the Susan G. Komen Breast Cancer Foundation grants BCTR0707323 to HGZ and BCTR0600484 to WEG.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.