Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy.

Exosomes are involved in cell-to-cell communication and play a crucial role in cellular physiology. The role of exosomes in cancer has been widely explored. Tumor cells have evolved and adapted to evade the immune response. The study of the immune system's modulations in favor of rogue tumor cells led to the development of a novel immunotherapeutic strategy targeting the immune checkpoint proteins (ICPs). In clinical settings, the response to ICP therapy has been inconsistent and is difficult to predict. Quantitating the targeted ICPs through immunohistochemistry is one approach, but is not pragmatic in a clinical setting and is often not sensitive. Examining the molecules present in bodily fluids to determine ICP treatment response, "liquid biopsy" is a convenient alternative. The term "liquid biopsy" refers to circulating tumor cells (CTCs), extracellular vesicles (EVs), non-coding (nc) RNA, circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), etc. EVs includes exosomes, microvesicles, and oncosomes. Herein, we focus on exosomes isolated from bodily fluids and their use in liquid biopsy. Due to their unique ability to transfer bioactive molecules and perturb the physiology of recipient cells, exosomes have garnered attention for their immune modulation role and as a resource to identify molecules associated with liquid biopsy-based diagnostic methods. In this review, we examine the putative role of exosomes and their cargo in influencing the immune system. We discuss the immune and tumor cells present in the tumor microenvironment (TME), and the exosomes derived from these cells to understand how they participate in creating the immune-suppressive TME. Additionally, use of exosomes in liquid biopsy-based methods to measure the treatment response elicited by immunotherapy is discussed. Finally, we describe how exosomes have been used to develop immune therapies, especially cell-free vaccines, for cancer treatment.