Abstract
Exosomes are lipid bilayer particles that originated from almost all types of cells and play an important role in intercellular communication. Tumor-derived exosomes contain large amounts of noncoding RNA, DNA, and proteins, which can be transferred into recipient cells as functional components in exosomes. These exosomal functional constituents depend on the originating cells, and it has been proved that types and numbers of exosomal components differ in cancer patients and healthy individuals. This review summarizes the role of tumor-derived exosomes in immunomodulation and discusses the application of exosomes in immunotherapy in cancers. Overall, exosomes isolated from cancer cells are turned out to promote immune evasion and interfere with immune responses in tumors through inducing apoptosis of CD8+ T cells, facilitating generation of Tregs, suppressing natural killer (NK) cell cytotoxicity, inhibiting maturation and differentiation of monocyte, and enhancing suppressive function of myeloid-derived suppressor cells (MDSCs). Mechanistically, exosomal functional components play a significant role in the immunomodulation in cancers. Moreover, based on the existing studies, exosomes could potentially serve as therapeutic delivery vehicles, noninvasive biomarkers, and immunotherapeutic vaccines for various types of cancers.
Highlights
Cancer is a global public health problem, and the incidence and mortality of cancer are dramatically increasing
Exosomes derived from hypoxic oral squamous cell carcinoma enhance immunosuppressive function of myeloid-derived suppressor cells (MDSCs) to interfere with moderation functions of γδ T cell via miR-21/phosphatase and tensin homolog (PTEN)/programmed death-ligand 1 (PD-L1) signaling pathway [99]
More than 150 unique exosomal miRNAs are identified in cancer patients, and hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b may be potential biomarkers to predict treatment efficacy of PD-1/PD-L1 immunotherapy in lung cancers [108]
Summary
Cancer is a global public health problem, and the incidence and mortality of cancer are dramatically increasing. Immune cells in tumor microenvironment play important roles in tumorigenesis [5], and exosomes released into tumor microenvironment have been proved to be able to regulate immune responses in tumors [6]. A subtype of extracellular vesicle, refers to lipid bilayer particles with a diameter of 50-150 mm [7]. They are released by almost all types of cells into microenvironment and have emerged as a novel method for intercellular communication through either functional component transfer or membrane receptor-mediated signaling transduction [8]. Exosomes isolated from cancer cells can interfere with immune responses and correlate with the development and progression of tumors, including tumor growth, invasion, and metastasis [11, 12]. This review is aimed at summarizing the functional components in exosomes, reviewing the role of tumor-derived exosomes in immunomodulation, and discussing the application of exosomes in immunotherapy in cancers
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