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Review
. 2022 Jan 18;13(1):64.
doi: 10.1038/s41419-022-04510-8.

Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion

Wanjia Tian #  1 , Ningjing Lei #  2 , Junying Zhou  1 , Mengyu Chen  1 , Ruixia Guo  1 , Bo Qin  3 , Yong Li  4   5   6 , Lei Chang  7
Affiliations
Review

Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion

Wanjia Tian et al. Cell Death Dis. .

Abstract

Chemoresistance and metastasis are the major challenges for the current ovarian cancer treatment. Understanding the mechanisms of ovarian cancer progression and metastasis is critically important for developing novel therapies. The advances in extracellular vesicles (EVs) research in recent years have attracted extensive attention. EVs contain a variety of proteins, RNAs, DNAs, and metabolites. Accumulating evidence indicates that ovarian cancer cells secrete a large amount of EVs, playing an important role in tumor progression and recurrence. In the microenvironment of ovarian tumor, EVs participate in the information transmission between stromal cells and immune cells, promoting the immune escape of ovarian cancer cells and facilitating cancer metastasis. Here, we review the recent advances of EVs in chemoresistance, mechanisms of metastasis, and immune evasion of ovarian cancer. Furthermore, we also discuss the challenges of EV research and future application of EVs as promising biomarker sources in response to therapy and in therapy-delivery approaches for ovarian cancer patients.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. EVs-mediated drug-resistance mechanism of OC.
Drug-resistant cells excrete chemotherapeutic drugs out of the cell by secreting EVs to achieve the purpose of chemotherapy resistance. At the same time, the ncRNA and active protein contained in the EVs secreted by the drug-resistant cells enter the sensitive cells through endocytosis, thereby transmitting the drug-resistant phenotype. We use EV miR-21 [49] as an example to demonstrate the emergence of this resistance mechanism. EVs secreted by drug-resistant cells also change the tumor microenvironment, making tumor cells more likely to survive.
Fig. 2
Fig. 2. The role of EVs in OC metastasis.
OC-derived EVs promote OC metastasis by promoting angiogenesis, affecting the EMT process, producing immunosuppression, directly stimulating OC cells, and participating in the construction of premetastatic niches. A It shows the general structure, size, content, and markers of EVs [22, 24]. B The VEGF carried by EVs binds to the VEGFR of vascular endothelial cells to promote angiogenesis [79]. C EVs promote the process of EMT [84]. D PD-L1 is expressed on the surface of EVs, which inhibits the activation of immune cells [120]. E EVs directly stimulate OC cells, causing them to metastasize [25]. F EVs are involved in the construction of the niche before OC peritoneal metastasis [96].
Fig. 3
Fig. 3. The role of EVs in OC immune evasion.
OC-derived EVs inhibit the activation of DC cells, induce the polarization of macrophages, inhibit the cytotoxicity of NK cells, and regulate the function of T cells. The miRNAs carried in EVs secreted by OC cells promote the conversion of macrophages into M2 phenotype [124], and the FasL carried on the surface induces the apoptosis of DCs [128]. EV cargo also inhibits the proliferation of CD4+ and CD8+ T cells through the presentation of DCs [145]. EV cargo directly stimulates T cells and NK cells as well as inhibits their functional activation [136, 144]. EVs help OC cells produce immune evasion through these mechanisms of action.
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