Abstract
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. This review aims 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.
Highlights
Cancer cells heterogeneity has a strong impact on tumor progression and metastasis, and tumor-associated stromal cells are a key player in this phenomenon.Cooperative cancer cell interaction with surrounding cells is mediated by several mechanisms of intercellular communication, including secretion of growth factors, cytokines and chemokines, and the production and release of extracellular vesicles (EVs)
Apicella and colleagues reported that in lung cancer and gastric cancer cells derived from patient tumors treated with tyrosine kinase inhibitors, there is an increase of glycolytic metabolism and lactate release that act as molecule driving cancer-associated fibroblasts (CAFs) to secrete more hepatocyte growth factor (HGF), which overcomes TKI inhibitory effects [36]
Intratumor heterogeneity appears to be regulated by intrinsic factors and by extrinsic factors related to tumor microenvironment such as cytokines, chemokine, growth factors, and EVs [135]
Summary
Cancer cells heterogeneity has a strong impact on tumor progression and metastasis, and tumor-associated stromal cells are a key player in this phenomenon. Wolf and colleagues initially considered EVs only as waste released by cells, growing evidence in the field has highlighted their role as signaling messengers in physiological and pathological processes, including cancer development [1]. Based on their biogenesis, EVs can be divided into two main categories comprising exosomes, which originate within the endosomal system, and microvesicles, that are shed from the plasma membrane.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
