Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors

Abstract

The tumour microenvironment (TME) plays a crucial role in the regulation of cell survival and growth by providing inhibitory or stimulatory signals. Extracellular vesicles (EV) represent one of the most relevant cell-to-cell communication mechanism among cells within the TME. Moreover, EV contribute to the crosstalk among cancerous, immune, endothelial, and stromal cells to establish TME diversity. EV contain proteins, mRNAs and miRNAs, which can be locally delivered in the TME and/or transferred to remote sites to dictate tumour behaviour. EV in the TME impact on cancer cell proliferation, invasion, metastasis, immune-escape, pre-metastatic niche formation and the stimulation of angiogenesis. Moreover, EV can boost or inhibit tumours depending on the TME conditions and their cell of origin. Therefore, to move towards the identification of new targets and the development of a novel generation of EV-based targeting approaches to gain insight into EV mechanism of action in the TME would be of particular relevance. The aim here is to provide an overview of the current knowledge of EV released from different TME cellular components and their role in driving TME diversity. Moreover, recent proposed engineering approaches to targeting cells in the TME via EV are discussed.

Keywords: EV engineering; extracellular vesicles; tumour microenvironment.

Figure 1

Extracellular vesicles (EV) in the tumour microenvironment (TME). Cancer cells, cancer associated fibroblasts (CAF), immune cells, stem cells and endothelial cells interact each other via EV in the TEM. EV can exert pro-tumour or anti-tumour effects to modulating proliferation, invasion, metastasis formation and angiogenesis.

Figure 2

Set-up phases of chimeric antigen receptor (CAR)-engineered T-cell (CAR-T) EV engineering. 1. T cells undergo collection through positive or negative selection methods from cancer patients’ peripheral blood sample. 2. T cells are transfected with CARs through viral or non-viral transfection technology. 3. CAR-engineered T cells are ex vivo expanded in the presence of IL-2. 4. CAR-T cell-derived EV undergo isolation. 5. EV can be re-infused in the patient after chemotherapy preconditioning.

Figure 3

EV-miRNA-loading. Specific miRNA displaying anti-cancer properties are loaded in EV and used for treatment. Engineered miRNA-EV despatch their anti-tumour effects by regulating apoptosis, proliferation, and angiogenesis.