Extracellular Vesicles in Cancer Immunosurveillance

The recent years of research has given rise to a huge body of evidence supporting the extensive roles of extracellular vesicles (EVs) in host-tumor interactions. While these nano-sized vesicles were initially praised for their inertness and stealth in terms of immunogenic properties, further research opened new windows on their immune-stimulating capabilities and great potential to be utilized as therapeutic tools in hopes of eliciting significant immune responses of therapeutic efficacy. This prospect started to shape with the initial reports that tumor-derived EVs could be potentially used as rich sources of tumor antigens to induce potent T cell responses capable of rejecting the inoculated tumors in mice models and continued to grow with the interesting use of MHC-bearing EVs, produced by antigen presenting cells, as novel EV-based vaccines for cancer. On the other side, the detection of important immune-regulating molecules such as PDL-1 and PD-1 on the surface of EVs of cancer cells revealed their role in promoting the immune evasion of cancer cells as parts of their escape mechanisms, which lie behind the insufficient treatment success of a group of drugs targeting these molecules i.e. check point inhibitors. Furthermore, therapeutic interventions targeting the vicious EV-mediated networks to promote anti-cancer immune responses are among other potentials of this field to be considered.

Given the controversial reports on the effects of EVs (tumor-derived and non-tumor derived) on cancer immune surveillance, this field still needs a great deal of attention. Specifically, based on a recent MISEV report, the majority of the previously conducted research in the field has not followed a unified methodology for the identification of EVs; hence, a large proportion of the controversies can be due to the absence of a clear consensus in defining the EVs in question. Therefore, understanding the roles of EVs in cancer immunosurveillance and the potential therapeutic opportunities are among the most interesting future visions. Delineating the dual role of tumor-derived EVs with regard to cancer immunity (their suppressing vs. stimulating nature) also needs to be extensively addressed. On such a basis, an exclusive Research Topic entitled “Extracellular vesicles in cancer immune surveillance” is suggested to call forth the most influencing scientists in the field to contribute their latest high quality research. This will, indeed, give rise to a valuable collection of latest advances in the field for a wide readership.

In this thematic issue we encourage the authors to submit Original Research, Reviews, and meta-analyses prepared rigorously and presenting novel findings on the most recent aspects of the field. The topics covered in this issue include but are not limited to:

- The role of extracellular vesicles (EVs) in regulating the tumor microenvironment and the immune response
- Different strategies to educate EV-producing cells to produce EVs with characteristics of interest
- Recent findings on the role of EVs on anti-tumor immunity: suppressive vs. stimulatory roles
- Novel marker-specific techniques for EV isolation and characterization
- Therapeutic opportunities regarding the use of EVs as vaccines or therapies for cancer treatment
- Recent findings on the possibility of therapeutic targeting of EVs in cancer

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.