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Recent advances in exosome-based cancer immunotherapy.

Yubin Zhou, Qun Zeng, Herbert Schwarz

Following the discovery of their immunological functions in 1996, exosomes have been re-classified from inconsequential cell garbage boxes to critical players in cell-cell communication [1-3]. Since then, extensive attention has been drawn to exosomes, resulting in a dramatic rise in publication numbers (Figure 1), and the initiation of clinical trials involving exosomes [4,5]. Currently, the biological functions of exosomes are not yet completely understood, but this seems not to dampen the enthusiasm of immunologists and clinicians in utilizing the unparalleled advantages of exosomes, which include the cell membrane-like structure, the carrier capacity for biomolecules and the capability of immunoregulation [6]. In recent years immunotherapy has demonstrated its potential as an effective alternative for cancer treatment, where conventional treatments like surgery, chemotherapy and radiation therapy failed or were of little effect [6,7]. Accumulating evidence has indicated that exosomes are involved in immunological activities (i.e. modulation of antigen presentation) and cancer development, suggesting exosomes may be a potential target for cancer immunotherapy [8-10]. Also, some exosome properties (i.e. concentration, composition) are cancer-dependent, for instance, the increased number in body fluids of cancer patients [11]. Inspired by these discoveries, exosomes have been explored and tested for cancer immunotherapy [1,8,12,13]. This review covers the current understanding of exosomes in composition, isolation and characterization, and highlights the state of the art of exosomebased cancer immunotherapy, including exosomal carriers, exosome-based immune regulators and engineered exosomes, with a discussion on challenges and future perspectives. Undoubtedly, approaches utilizing exosomes for cancer immunotherapy will only increase in numbers in the future.