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.

Fig. 1

Demonstration of how neoplastic lesions inhibit the immune system by the release of exosomes. Exosomes inhibit the number and actions of NK cells shown by the blockage of the pathway between NK cells and the tumor. Similarly, exosomes inhibit the number of T cells that can infiltrate tumors. Also shown are the interaction of exosomes with monocytes and immature DC, which prevents both from forming mature DC. The decrease in DC, NK cells and T cells in the tumor causes a reversal in the cell death usually caused by these cells and results in a decrease in immune system-induced death of neoplastic cells and growth of the tumor.