Extracellular Vesicles and Cancer – A Focus on Metabolism, Cytokines, and Immunity

A better understanding of the mechanisms of cell communication between cancer cells and the tumor microenvironment is crucial to develop personalized therapies. It has been known for a while that cancer cells are metabolically distinct from other non-transformed cells. This metabolic phenotype is not peculiar to cancer cells but reflects the characteristics of the tumor microenvironment. Recently, it has been shown that extracellular vesicles are involved in the metabolic switch occurring in cancer and tumor-stroma cells. Moreover, in an immune system, the metabolic programs of different cell subsets are distinctly associated with their immunological function, and extracellular vesicles could be a key factor in the shift of cell fate modulating cancer immunity. Indeed, during tumor progression, tumor-associated immune cells and fibroblasts acquire a tumor-supportive and anti-inflammatory phenotype due to their interaction with tumor cells and several findings suggest a role of extracellular vesicles in this phenomenon. Researchers at the Catholic University of the Sacred Heart, Rome aim to collect all the available evidence so far obtained on the role of extracellular vesicles in the modulation of cell metabolism and immunity. Moreover, we discuss the possibility for extracellular vesicles of being involved in drug resistance mechanisms, cancer progression and metastasis by inducing immune-metabolic effects on surrounding cells.

Immunity and extracellular vesicles in cancer

Schematic view of how T-sEVs repress the function of NK, T, and dendritic cells (DC) and activate the populations of myeloid-derived suppressive cells (MDSCs), regulatory T cells (Treg) while skewing macrophage function toward the M2 phenotype. PD-L1 packaged in T-sEVs is transferred to dendritic cells or macrophages which then block T cell function.