Recent advances on the role of tumor exosomes in immunosuppression and disease progression

Abstract

Exosomes are endosomal-derived nanovesicles released by most cells types, including tumor cells, and principally involved in intercellular communication in physiology and disease. Tumor exosomes are gaining increasing interest in medicine and oncology as efficient tools for the delivery of defined signals. Representing the acellular replicas of tumor cells, they contain a great variety of bioactive molecules, such as proteins, RNA, miRNA and DNA. Their great ability to recirculate in body fluids and their structure allow them to transport their cargo to distant targets. Major studies have shown that tumor exosomes convey information not only between tumor cells but also to other cell types, including different immune cell components. There is increasing evidence that these nanovesicles may contribute to cancer progression by influencing different immune cell types, likely blunting specific T cell immunity and skewing innate immune cells toward a pro-tumorigenic phenotype. Because of this function and the additional property to deliver molecular signals modulating neoangiogenesis and stroma remodeling, tumor exosomes are believed to play a role in tumor progression by favoring metastatic niche onset. This review outlines the recent knowledge on immune suppressive mechanisms mediated by tumor exosomes. We will discuss our view on the role of these nanovesicular structures in cancer progression and how their presence could interfere with cancer therapy.

Body Fluid Exosomes Promote Secretion of Inflammatory Cytokines in Monocytic Cells via Toll-like Receptor Signaling

“…However, significantly enhanced levels of exosomes are found in the sera or AS of cancer patients, and the amount is often correlated with the stage of the disease (12,39,40). There is evidence that exosomes released by the tumor can suppress the immune system of the patient and prepare niches for metastatic spread (41). In the present report we have asked how exosomes can interact and stimulate immune cells using monocytic THP-1 cells as a model.…”

Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment

“…17 Sucrose gradient analysis For sucrose density gradient fractionation, vesicles were loaded on top of a stepwise sucrose gradient at the following concentrations: 2 M, 1.3 M, 1.16 M, 0.8 M, 0.5 M and 0.25 M in TBS. The gradient was centrifuged for 2.5 h at 100.000 £ g, 4 C using a Beckman SW40 Rotor (k-factor: 137). 300 g of total protein were applied to each sucrose gradient and twelve 1 mL fractions were collected from the top of the gradient, diluted with TBS (1:10) and ultra-centrifuged for 2,5 hrs at 100.000 £ g. The resulting pellet was treated with RNAseA to eliminate any free RNA.…”

“…1 Recent data suggest a central role of tumor-derived EVs in numerous processes impacting tumor growth such as promoting metastasis, 2,3 inducing drug resistance and to skew the differentiation of monocytes into MDSCs, 4,5 that strongly suppress antitumor immunity promoting cancer progression. Conceptually, the interaction of tumor cells with the host tissue has been based on the interplay of individual pairs of ligands and their receptors impacting their gene regulation.…”

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

“…All these factors exert their effects in combination and in dose-dependent manner. They can affect myeloid cells both directly in tumor lesions and upon transportation to hematopoietic organs by tumor-derived exosomes or in soluble form by skewing the normal myeloid cell differentiation in the favor of MDSCs [22,26,53,54].…”