Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Hao, Qiongyu; Wu, Yong; Wu, Yanyuan; Wang, Piwen; Vadgama, Jaydutt V.

doi:10.3390/ijms23031461

Cited by 37 publications

(28 citation statements)

References 192 publications

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“…A large and rapidly growing body of evidence suggests that tumour cell-derived EVs interact with cells of the immune system in the tumour microenvironment, with an important role for EV-encapsulated miRNAs. We do not discuss the involvement of miRNAs in detail here and, instead, refer readers to a recent review of the topic 106 . Tumour cell-derived EVs mainly suppress antitumour immune responses through their effects on NK cells, T cells, DCs, macrophages, myeloid-derived suppressor cells (MDSCs) and regulatory B cells.…”

Section: Antitumour Responsesmentioning

confidence: 99%

The roles of extracellular vesicles in the immune system

2022

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The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.

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Section: Antitumour Responsesmentioning

confidence: 99%

The roles of extracellular vesicles in the immune system

2022

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“…Immune cells are critical antitumor effectors in the TME 13 , 14 . Suppressing T-cell proliferation and inhibiting CD8 T-cell activation, TDEs contribute to immune escape 15 , 16 . In addition, TDEs may also induce T-cell differentiation into a suppressive regulatory T-cell (Treg) phenotype, favoring immunosuppression 17 – 19 .…”

Section: Introductionmentioning

confidence: 99%

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Chen

Duan

et al. 2022

Exp Mol Med

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Mounting evidence indicates that tumor-derived exosomes (TDEs) play critical roles in tumor development and progression by regulating components in the tumor microenvironment (TME) in an autocrine or paracrine manner. Moreover, due to their delivery of critical molecules that react to chemotherapy and immunotherapy, TDEs also contribute to tumor drug resistance and impede the effective response of antitumor immunotherapy, thereby leading to poor clinical outcomes. There is a pressing need for the inhibition or removal of TDEs to facilitate the treatment and prognosis of cancer patients. Here, in the present review, we systematically overviewed the current strategies for TDE inhibition and clearance, providing novel insights for future tumor interventions in translational medicine. Moreover, existing challenges and potential prospects for TDE-targeted cancer therapy are also discussed to bridge the gaps between progress and promising applications.

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“…However, a previous study on TA exosomes revealed that the intracellular components included in exosomes can be exposed to immune cells without cell death ( 30 ). In addition, the tumor-derived exosomes can stimulate or suppress immune responses ( 30 , 31 ). As described above, the XC246 antigen appears to be a post-translationally modified BRD2 mainly localized in the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide‑conjugated BSA

et al. 2022

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Tumor-associated (TA) autoantibodies are considered to be promising biomarkers for the early detection of cancer, prior to the development of clinical symptoms. In the present study, a novel TA autoantibody was detected, which may prove to be useful as a diagnostic marker of human HCC using an HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) mouse model. Its target antigen was identified as the bromodomain-containing protein 2 (BRD2), a transcriptional regulator that plays a pivotal role in the transcriptional control of diverse genes. BRD2 was upregulated in HCC tissues of the H-ras12V-tg mouse and human subjects, as demonstrated using western blotting or immunohistochemical analysis, with the BRD2 autoantibody. In addition, the truncated BRD2 reactive to the BRD2 autoantibody was detected in tumor cell-derived exosomes, which possibly activated TA immune responses and the generation of autoantibodies. For the detection of the serum BRD2 autoantibody, epitope mimicries of autoantigenic BRD2 were screened from a random cyclic peptide CX 7 C library with the BRD2 autoantibody. A mimotope with the sequence of CTSVFLPHC, which was cyclized by one pair of cysteine residues, exhibited high affinity to the BRD2 autoantibody and competitively inhibited the binding of the autoantibody to the cellular BRD2 antigen. The use of this cyclic peptide as a capture antigen in human serum enzyme-linked immunosorbent assay allowed the distinction of patients with HCC from healthy subjects with 64.41% sensitivity and 82.42% specificity (area under the ROC curve, 0.7761), which is superior to serum alpha-fetoprotein (AFP; 35.83% sensitivity; 100% specificity; area under the ROC curve, 0.5337) for the diagnosis of HCC. In addition, the detection of the BRD2 autoantibody combined with other autoantibody biomarkers or AFP has increased the accuracy of HCC diagnosis, suggesting that the combinational detection of cancer biomarkers, including the BRD2 autoantibody, is a promising assay for HCC diagnosis.

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Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Cited by 37 publications

References 192 publications

The roles of extracellular vesicles in the immune system

The roles of extracellular vesicles in the immune system

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide‑conjugated BSA

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