We are analyzing https://link.springer.com/article/10.1186/s12943-021-01448-x.

Title:
Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC | Molecular Cancer
Description:
Background CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. Methods The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. Results The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. Conclusions Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
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Keywords {🔍}

circusp, cells, nsclc, expression, cell, pubmed, patients, cancer, article, shp, exosomes, tissues, fig, google, scholar, exosomal, cas, plasma, tumour, results, levels, antipd, immune, mice, central, data, circrnas, supplementary, rna, ncih, resistance, derived, lung, modified, function, progression, promotes, transfection, level, chen, human, correlation, blood, showed, additional, negative, compared, lines, luciferase, file,

Topics {✒️}

yong-bing wu conceived yong-bing wu wrote circular ubiquitin-specific protease-7 nci-h460-mock cell-derived tissues anti-cd3/anti-cd28 antibodies small-cell lung cancer plo5-cir-circusp7 overexpression vector yong-bing wu cell-type specific features wild-type shp2 sequence nci-h460 cell-derived exosomes specific pathogen-free conditions plo5-cir-mock vector wild-type circusp7 sequence article download pdf intra-tumoral niche maintains tumor-derived exosomal mirna received anti-pd1 immunotherapy enzyme-linked immunosorbent assay exosomal circusp7/mir-934/shp2 axis hcd34+-purified hpscs derived mir-145-5p/cxcl3 axis [14] mir-145-5p/cxcl3 axis anti-pd1 immunotherapy resistance circusp7-short hairpin rna circular rna circ-cpa4/ mutated mir-934-binding site promotes antitumor immunity healthy donor-derived cd8+ cell receptor-mediated signaling usp7-derived circrnas released oncogenic kras-driven tumours nci-h1299 cell lines pd-1 immunoreceptor inhibits anti-pd-1 treatment cycles anti-pd1 treatment cycles exosome-based treatment methods nsclc cell-derived exosomes high-resolution tem image targeting deubiquitination-related usp7 cell-related immune escape circusp7 inhibits ifn-γ shorter survival time membrane-bound extracellular vesicles exosome-mediated intercellular communication generate probe-coated beads full access cell-dependent manner specific molecular targets cell isolation kit

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         description:CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
         datePublished:2021-11-09T00:00:00Z
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            Oncology
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      description:CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
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         Exosome
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         Oncology
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      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
      name:Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China
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