Exosomes in Cancer: Circulating Immune-Related Biomarkers

Abstract

Exosomes, the smallest vesicles (30–100 nm) among multivesicular bodies, are released by all body cells including tumor cells. The cargo they transfer plays an important role in intercellular communication. Tumor-derived exosomes (TEXs) maintain interactions between cancer cells and the microenvironment. Emerging evidence suggests that tumor cells release a large number of exosomes, which may not only influence proximal tumor cells and stromal cells in the local microenvironment but can also exert systemic effects as they are circulating in the blood. TEXs have been shown to boost tumor growth promote progression and metastatic spread via suppression or modification of the immune response towards cancer cells, regulation of tumor neo-angiogenesis, pre-metastatic niche formation, and therapy resistance. In addition, recent studies in patients with cancer suggest that TEXs could serve as tumor biomarker reflecting partially the genetic and molecular content of the parent cancer cell (i.e., as a so-called “liquid biopsy”). Furthermore, recent studies have demonstrated that exosomes may have immunotherapeutic applications, or can act as a drug delivery system for targeted therapies with drugs and biomolecules.

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

“…Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression; one of these strategies is a release of exosomes [ 4 , 5 ]. Tumor cells, as well as immune cells, secrete exosomes that affect the activation of immune cells and immune surveillance [ 6 ]. Exosomes, harboring various cargoes that can accelerate angiogenesis, play an important role in cancer invasiveness [ 7 ].…”

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

“…Tumor-derived exosomes (TEX) promote cancer progression via modification or suppression of the immune response and therapy resistance and may have immunotherapeutic applications [11]. TEX are involved in regulating peripheral tolerance in patients with cancer [12] and may serve as tumor biomarkers [13].…”

Role of Chronic Lymphocytic Leukemia (CLL)-Derived Exosomes in Tumor Progression and Survival

“…Several proteins, such as CD63, CD81, CD9, TSG-101, Syndecan-1, MHC molecules, ALIX, HSP70 and BCR, are located on the surface of exosomes or included as cargo of exosomes and may represent markers of the paternal cell [44][45][46][47][48]. The composition and quantity of cargo components can differ between the normal and disease-associated exosomes [49][50][51]. This evidence suggests that the exosomes derived from pathological cells may be involved in pathogenesis of the disease and be considered a potential diagnostic and/or prognostic tool.…”