Exosome-Mediated Crosstalk Between Tumor and Tumor-Associated Macrophages

Abstract

Exosomes are nanosized vesicles, derived from the endolysosomal compartment of cells and can shuttle diverse biomolecules such as nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their origin cells. Delivery of these cargoes to recipient cells enables exosomes to influence diverse cellular functions. As one of the most abundant immune cells in the tumor microenvironment, tumor-associated macrophages (TAMs) are educated by the tumor milieu, which is rich in cancer cells and stroma components, to exert functions such as the promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Herein, we focus on exosomes-mediated intercellular communication between tumor cells and TAM in the tumor microenvironment, which may provide new targets for anti-tumor treatment. In this review, we highlight the most recent studies on the effect of tumor/macrophage-derived exosomes on macrophage/tumor function in different cancer types.

Impact of Storage Conditions on EV Integrity/Surface Markers and Cargos

“…The following studies also confirmed that all eukaryotes and prokaryotes could produce EVs, and it was considered that cells used these EVs as cargo transporters to transfer unwanted materials outwards [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. However, recent research has shown that EVs are crucial for intercellular communication throughout normal and pathological development [ 11 , 12 , 13 , 14 , 15 ]; in fact, some of them are involved in cancer progression [ 16 , 17 , 18 , 19 ], obesity and metabolic diseases [ 20 , 21 , 22 , 23 , 24 ], inflammatory and autoimmune pathogenesis [ 25 , 26 , 27 ]. Nowadays, various studies revealed that EVs are used in several clinical applications such as disease diagnosis and development of vaccines, drug distribution, and extracellular vesicle (EV)-based therapies [ 17 , 18 , 19 ].…”

“…However, recent research has shown that EVs are crucial for intercellular communication throughout normal and pathological development [ 11 , 12 , 13 , 14 , 15 ]; in fact, some of them are involved in cancer progression [ 16 , 17 , 18 , 19 ], obesity and metabolic diseases [ 20 , 21 , 22 , 23 , 24 ], inflammatory and autoimmune pathogenesis [ 25 , 26 , 27 ]. Nowadays, various studies revealed that EVs are used in several clinical applications such as disease diagnosis and development of vaccines, drug distribution, and extracellular vesicle (EV)-based therapies [ 17 , 18 , 19 ]. Electron microscopic imaging and nanoparticle tracking analysis (NTA) are the primary tools for the characterization of the morphology and size of vesicles.…”

Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a β-Blocker Potentiate Doxorubicin’s Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer

“…M1 macrophages display important antitumor activities and are involved in the immune system’s response to cancer, whereas M2 macrophages (also known as tumor-associated macrophages or M2-TAMs) promote cancer progression and contribute to multidrug resistance in cancer therapy [ 5 , 6 ]. Therefore, multiple antitumoral approaches are being explored to induce the shift of M2-TAMs to proinflammatory M1 macrophages [ 7 , 8 , 9 ]. Among the new immunotherapeutic treatments, approaches based on extracellular vesicles (EVs) are receiving attention for their antitumor potential and the bioengineering possibilities that they can offer [ 10 , 11 , 12 ].…”

“…EVs derived from M1 macrophages have demonstrated important antitumor properties against different types of cancer, including melanoma and breast cancer [ 18 ]. M1-derived EVs (M1-EVs) repolarize M2 macrophages and activate the resident M1 macrophages, thereby creating a proinflammatory TME that decreases tumor growth and induces apoptosis in cancer cells [ 7 , 8 ]. M1-EVs are also efficient adjuvants and nanocarriers that enhance the anticancer properties of cytostatic drugs and monoclonal antibodies in vitro and in vivo [ 8 , 19 ].…”

“…M1-derived EVs (M1-EVs) repolarize M2 macrophages and activate the resident M1 macrophages, thereby creating a proinflammatory TME that decreases tumor growth and induces apoptosis in cancer cells [ 7 , 8 ]. M1-EVs are also efficient adjuvants and nanocarriers that enhance the anticancer properties of cytostatic drugs and monoclonal antibodies in vitro and in vivo [ 8 , 19 ]. Evidence has suggested that hyaluronic acid (HA) can be used to increase targeting through the CD44 receptor and promote antitumor macrophage polarization [ 20 , 21 , 22 ].…”