The role of exosomes in the immune microenvironment of ovarian cancer

Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.

Exosomes cross-talk with immune cells in ovarian cancer immune microenvironment

Exosomes have a dual role in tumor immunity. (1) Exosomal miRNA induce M2-like macrophages (TAMs) to promote the progression of ovarian cancer, and macrophage-derived exosomes to exert the antitumor effect via miR-7. TAM-derived exosomes regulate the ratio of Treg/TH17. (2) Ovarian cancer cell-derived exosomes induce T cell apoptosis by Fas/FasL and FasL/CD3, and active T cell by presenting tumor antigens. (3) Ovarian cancer cell-derived exosomes induce DC apoptosis by Fas/FasL, DC-derived exosomes express MHCII, CD86 and ICAM1 to active T cell. (4) Ovarian cancer cell-derived exosomes enhance the migration of MSC, and exosomes derived from MSC upregulate pro-apoptotic signaling molecules (BAX, CASP9 and CASP3) to inhibit the progression of ovarian cancer. (5) Ovarian cancer cell-derived exosomes downregulate the killing effect of NK cell, NK cell-derived exosomes express NKG2D/DNAM-1 to kill the tumor cell and antitumor protein (CD56), FasL, perforin, granulysin, granzyme A and B. miR, microRNA; TAM, tumor-associated macrophages; DC, dendritic cells; MHC, major histocompatibility complex; NKG2D/DNAM-1, natural killer group 2, member D/DNAX accessory molecule-1; MSC, mesenchymal stem cells; CASP, caspase; OC, ovarian cancer.

Li X, Liu Y, Zheng S, Zhang T, Wu J, Sun Y, Zhang J, Liu G. (2021) Role of exosomes in the immune microenvironment of ovarian cancer. Oncol Lett 21(5):377. [article]

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