Morphological and molecular features of TEX

Introduction Exosomes, small membrane-bound vesicles, are a class of extracellular vesicles (EVs) made and released by most, if not all, cells. They are present in all body fluids (1–4) and have recently been in the limelight because of their potential role as communication vehicles between cells and as a new, noninvasive type of cancer biomarker (5–7). My first encounter with tumor-derived exosomes (TEX) occurred in the early 2000s, when an observation that sera of cancer patients induced DNA fragmentation in human activated primary T cells attracted my attention. Sera of healthy donors did not induce apoptosis of activated CD8+ T cells (8). Upon ultracentrifugation of cancer patients’ sera, it turned out that the pelleted vesicular material contained apoptosis-inducing factors. Later, it became clear that small vesicles sized at approximately 100 nm (i.e., virus size) and carrying FasL were responsible for apoptosis of activated, FAS-expressing T cells (8). Studies of this phenomenon using cultured tumor cells showed that these vesicles were produced in abundance and induced a variety of functional alterations in immune cells. Exosome secretion by cells seems to be a physiological phenomenon that occurs spontaneously. In fact, in the early 1980s, exosome secretion was thought to be necessary to remove cellular waste (9). On the basis of studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer (10). TEX carry a cargo of molecules that is different from that of exosomes made by normal cells and, consequently, TEX mediate distinct biological effects (11). This Review will consider TEX, their cargo, and biological functions in the context of tumor-mediated immune suppression, which accompanies tumor growth and facilitates tumor escape from the host immune system (12).