The exosomes in tumor immunity - PubMed (original) (raw)

Review

The exosomes in tumor immunity

Yanfang Liu et al. Oncoimmunology. 2015.

Abstract

Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4+ and CD8+ T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4+ and CD8+ Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DC-derived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

Keywords: exosomes; extracellular vesicle; immunosuppression; intercellular communication; tumor immunity; tumor vaccine.

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Figures

Figure 1.

Figure 1.

Exosome-mediated immunosuppression of tumor immunity. Exosomes derived from cancer cells have been shown to be involved in the modulation of tumor immunity in various ways: (A) Inhibition of proliferation and differentiation of CD4+ T cells into Th1 and Th17, inhibition of cytotoxicity of CTLs, NK cells and macrophages, inhibition of differentiation and maturation of DCs. (B) Promotion of CD4+, CD8+ Tregs and Bregs generation, induction of myeloid precursor differentiation into MDSCs, alternative activation of macrophages.

Figure 2.

Figure 2.

Strategies for exosome-based tumor immunotherapy. This figure presents two main strategies for application of exosomes in tumor therapeutics. Exosomes secreted from antigen-loaded DCs carry functional peptide-MHC complexes, co-stimulatory and adhesion molecules and induce activation of CD4+ T cells, CD8+ T cells and NK cells, thus mediating cytotoxicity to tumor cells and inhibition of tumor growth. These molecules can also be exchanged between DCs to induce antitumor immune response indirectly. Additionally, tumor-derived exosomes (TEXs) carry tumor antigens and can trigger efficient antigen presentation of APCs, thus being used as resources of tumor antigens to prepare tumor vaccines. Moreover, modification of TEXs is developed to improve their immunogenicity, such as genetic engineering stress and protein loading.

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