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Tumor cell-derived extracellular vesicles (TEVs) are an important means of tumor communication with, and manipulation of, the patient’s physiology. TEVs influence the local tumor environment as well as the systemic conditions of the patient. Progressive changes in tumor interactions with the host immune system are defined as “immunoediting”. Here, we summarize TEV effects on the immune system during the stages of cancer immunoediting and outline the molecular and cellular characteristics of interactions that result in complete tumor regression versus tumor immune escape and progression. Generally, the cargo profile of TEVs naturally changes during immunoediting toward immunosuppression while different cell stress or treatment conditions can inhibit this process or even reverse it to immunostimulation by altering the TEVs cargos. Therefore, understanding potential immunotherapeutic properties and how they can be manipulated to treat cancer should be considered a new research approach in oncoimmunotherapy.

The tumor microenvironment (TME) within and around a tumor is a complex interacting mixture of tumor cells with various stromal cells, including endothelial cells, fibroblasts, and immune cells. In the early steps of tumor formation, the local microenvironment tends to oppose carcinogenesis, while with cancer progression, the microenvironment skews into a protumoral TME and the tumor influences stromal cells to provide tumor-supporting functions. The creation and development of cancer are dependent on escape from immune recognition predominantly by …