Roles of exosomal circRNAs in tumour immunity and cancer progression

Abstract

Tumour immunity plays an important role in the development of cancer. Tumour immunotherapy is an important component of antitumour therapy. Exosomes, a type of extracellular vesicle, act as mediators of intercellular communication and molecular transfer and play an essential role in tumour immunity. Circular RNAs (circRNAs) are a new type of noncoding RNA that are enriched within exosomes. In this review, we describe the effects of exosomal circRNAs on various immune cells and the mechanisms of these effects, including macrophages, neutrophils, T cells, and Natural killer (NK) cells. Next, we elaborate on the latest progress of exosome extraction. In addition, the function of exosomal circRNAs as a potential prognostic and drug sensitivity marker is described. We present the great promise of exosomal circRNAs in regulating tumour immunity, predicting patient outcomes, and evaluating drug efficacy.

Fig. 1. Diagram of the effects of exosomal circRNAs on macrophages.

CircRNAs are transported into macrophages through exosomes. They sponge certain miRNAs to improve the expression of the genes involved. They also affect signalling pathways to function. The end result is to regulate macrophage M2 polarization.

Fig. 2. Effects of exosomal circRNAs on immune checkpoints and T cells.

CircRNAs sponge specific miRNAs as they enter cancer cells or T cells, increasing PDL1/PD1 expression. After PD1 was combined with PDL1, the activity and proliferation of T cells decreased significantly.

Fig. 3. Effects of exosomal circRNAs on NK cells and neutrophils.

A Exosomal circPACRGL derived from cancer cells sponges miR-449c-5p to increase the expression of TIM-3. This results in the exhaustion of NK cells. B Exosomal circPACRGL sponges miR-142-3P or miR-506-3P and increases the expression of TGF-β. This leads to an increase in the neutrophil N2 phenotype.