Impact of Chemotherapy on Extracellular Vesicles: Understanding the Chemo-EVs

Abstract

Chemotherapy is the standard go-to treatment for cancer besides surgery and radiation. It has recently come to light that the interaction between chemotherapy and the immune system is important in maintaining tumor immunity as well as influencing the efficacy of the therapy. However, ample preclinical studies have shown that in addition to direct cytotoxic effects on cancer cells, a fraction of chemotherapeutic agents may promote immunogenic cell death, and alter the inflammatory milieu of the tumor microenvironment. Extracellular vesicles (EV) have been shown to interact with the tumor microenvironment by delivering alterative signals to the surrounding cells; as a result, this results in interference with each cell's capability to eradicate tumors or gives advantages to cancer cells so as to survive therapy. Chemotherapy-induced extracellular vesicles (chemo-EVs) have been theorized to be carrying different cargo loads than non-chemotherapy-induced EVs. Aside from chemoresistance, there is growing evidence to suggest that chemo-EVs could dictate tumor behavior, especially in terms of metastasis, immune response, and cancer stemness. This mini-review attempts to summarize and evaluate recent developments on the role of chemo-EVs in other aspects of tumor-related processes.

Keywords: cancer; drug; exosome; microvesicle; therapy.

Figure 1

Overall schematic representation on the complex properties of chemo-EVs. (A) The number of released EVs could be dependent on the duration of drug stimulation. (B) Immunomodulating effects of chemo-EVs (e.g., reduced immune checkpoint markers such as PDL-1, activated inflammasome, and stimulate natural killer cells). Nevertheless, the uncertainty between the immunosuppressive and immunoactivator capabilities of chemo-EVs warrants further investigation. (C) Chemo-EVs affect other tumor biological processes such as cell proliferation and cell viability through the different cargoes that it carries. (D) The heterogeneity of chemo-EVs needs further elucidation to better understand the role of chemo-EVs.