Exosome‐mediated regulation of tumor immunology

Seo, Naohiro; Akiyoshi, Kazunari; Shiku, Hiroshi

doi:10.1111/cas.13735

Cited by 119 publications

(88 citation statements)

References 60 publications

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“…Infiltrating normal cells are involved in constructing the tumor structure and build the tumor microenvironment that actively contributes to cancer progression by promoting angiogenesis, metastasis, and suppression of the anti-cancer immune response [59,60]. These cells in the tumor microenvironment include cancer-associated fibroblasts (CAFs) with properties differentiated from mesenchymal stem cells (MSCs) [61], tumor-associated immune cells including CD11b+ immune cells such as tumor-associated macrophages (TAMs) [62][63][64] and myeloid-derived suppressor cells (MDSCs) [65], tumor-infiltrating dendritic cells (DCs) [66], monocytes [67], T cells including cytotoxic T lymphocytes (CTLs) and tumor-infiltrating regulatory T cells (TITreg) [68], B cells [69], tumor endothelial cells (TECs) [70,71], adipocytes [72][73][74][75], and normal epithelial cells [76]. Such stromal cells communicate with each other and tumor cells using cytokines, growth factors, MMPs, ECM, microRNAs, and EVs.…”

Section: Stroma-derived Evs In Tumor Progressionmentioning

confidence: 99%

“…Disrupting the interaction of the PD-L1 ligand with the PD-1 receptor on T cells restores T cell-mediated immune responses and potentiates anti-tumor immunity ( Figure 4b). However, not all patients respond to such immune checkpoint inhibitors, as exosomes secreted by tumor cells carry bioactive PD-L1 on their surface and can thus suppress the immune response [76] (Figure 4c). EVs were found to capture the anti-PD-L1 antibody and display it on their surface thereby engaging with PD-1 on tumor-specific T cells [154].…”

Section: Extracellular Vesicles As Immunosuppressive Agentsmentioning

confidence: 99%

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A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

Eguchi

Taha

Calderwood

et al. 2020

Biology

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Extracellular vesicles (EVs), such as exosomes or oncosomes, often carry oncogenic molecules derived from tumor cells. In addition, accumulating evidence indicates that tumor cells can eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing drug resistance phenotype is often coupled with cellular dedifferentiation and transformation in cells undergoing epithelial-mesenchymal transition (EMT), and the adoption of a cancer stem cell phenotype. The release of EVs is also involved in immunosuppression. Herein, we address different aspects by which EVs modulate the tumor microenvironment to become resistant to anticancer and antibody-based drugs, as well as the concept of the resistance-associated secretory phenotype (RASP).

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Section: Stroma-derived Evs In Tumor Progressionmentioning

confidence: 99%

Section: Extracellular Vesicles As Immunosuppressive Agentsmentioning

confidence: 99%

A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

Eguchi

Taha

Calderwood

et al. 2020

Biology

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“…We previously identified LOXL2 as a candidate factor that could induce pre‐metastatic niche formation in a target lymph node of HNSCC metastasis . Based on the predicted roles of exosomes, which include altering signal transduction between cells and tissues, using exosomes to transport LOXL2 fits well with the concept of exosome‐mediated tumor progression . If LOXL2 is important in establishing pre‐metastatic niche formation, LOXL2 may be dispensable for metastasized tumor cells once premetastatic niches are established; hence, LOXL2 may not be expressed by metastasized tumor cells at metastatic lesions.…”

Section: Discussionmentioning

confidence: 91%

Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma

et al. 2019

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Objectives: The secretory enzyme lysyl oxidase like 2 (LOXL2) is speculated to contribute to tumor progression through its functions in the remodeling of extracellular matrix and epithelial-mesenchymal transition. We previously identified elevated expression of LOXL2 in metastatic human head and neck squamous cell carcinoma (HNSCC) cells in a mouse lymph node metastases model. Here we performed a case series study examining LOXL2 expression levels in human serum from HNSCC patients to evaluate whether LOXL2 is worth evaluation in a large cohort study.Methods: LOXL2 protein levels in three serum samples from HNSCC patients were assessed by immunoblotting and LOXL2 tissue expression was examined in one human tongue squamous cell carcinoma (SCC) tissue by immunohistochemistry as a representative of HNSCC tissue. Serum samples were further fractionated in exosomes and supernatants by ultracentrifugation, which were then subjected to immunoblot and in vitro LOX activity analyses. Exosomal LOXL2 levels of 36 serum samples from HNSCC patients and seven healthy volunteers were measured using polymer sedimentation exosome preparation followed by ELISA measurement and subjected to statistical analyses.Results: Immunoblot analyses revealed that LOXL2 was present in serum exosomal fractions from three HNSCC patients, and we observed approximately threefold higher levels of LOXL2 in HNSCC patients compared with three healthy volunteers. Immunohistochemical LOXL2 staining was detected in HNSCC cells in addition to non-cancerous lipid tissues and some muscles in human tongue HNSCC tissue. Further measurements of exosomal LOXL2 by ELISA showed over ninefold higher mean LOXL2 levels in patients compared with controls. Statistical analysis revealed a correlation between elevated serum exosomal LOXL2 levels and low-grade, but not high-grade, HNSCC.Conclusions: Our case series study that elevated serum exosomal LOXL2 levels exhibited a correlation with low-grade HNSCCs. A follow-up large cohort clinical study will be required to determine the potential clinical utility of LOXL2 as a new biomarker and/or therapy target for HNSCCs.

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“…In addition, exosomes are also involved in the regulation of the tumor immune response [45]. Tumor cell exosomes can promote the production of prostaglandin E2, IL-6 and TGF-β by myeloid-derived suppressor cells (MDSCs), thus forming a powerful immune suppression environment in tumor lesions [46].…”

Section: Discussionmentioning

confidence: 99%

Based on Exosome-Derived Genes for Constructing Diagnostic, Prognostic and Recurrence Models and Predicting Therapeutic Response for Hepatocellular Carcinoma

Ji¹,

Tang²,

Zhu³

et al. 2020

Preprint

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Background: In this study, we performed a comprehensive analysis to identify the optimal gene set derived from exosomes in hepatocellular carcinoma (HCC) with great prognostic value to construct prognostic, recurrence and diagnostic models and predicted therapeutic response for hepatocellular carcinoma.Methods: Differential expression analysis and Weighted Gene Co-Expression Network Analysis (WGCNA) of RNA-sequencing were used to identify differentially expressed exosome-derived genes related to HCC. Univariate and multivariate Cox regression analyses were performed to determine exosome-derived genes associated with prognosis of HCC to construct a prognostic model, and recurrence and diagnostic models were built based on the same genes. Results: MYL6B and THOC2 were determined to be closely related to prognosis in HCC. The prognostic and recurrence models built based on these two genes were confirmed to be independent predictive factors with superior predictive performance. Patients with high prognostic risk had poorer prognosis than patients with low prognostic risk in all HCC sets, namely, the TCGA cohort (HR=2.5, P<0.001), ICGC cohort (HR=3.15, P<0.001) and GSE14520 cohort (HR=1.85, P=0.004). A higher recurrence probability was found in patients with high recurrence risk than in patients with low recurrence risk in the HCC sets of the TCGA cohort (HR=2.44, P<0.001) and GSE14520 cohort (HR=1.54, P=0.025). High prognostic risk patients had higher expression of immune checkpoints, such as PD1, B7H3, B7H5, CTLA4 and TIM3 (P<0.05). Patients with higher prognostic risk showed higher resistance to some chemotherapy and targeted drugs, such as methotrexate, erlotinib and vinorelbine (P<0.05). The diagnostic models based on the same two genes were determined to accurately distinguish HCC from normal subjects and dysplastic nodules.Conclusions: Prognostic, recurrence, and diagnostic models based on the two exosome-derived genes (MYL6B and THOC2) were proven superior predictive performance. Our findings lay the foundation for identifying molecular markers to increase the early detection rate of HCC, improve disease outcomes, and determine more effective individualized treatment options for patients.

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Exosome‐mediated regulation of tumor immunology

Cited by 119 publications

References 60 publications

A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma

Based on Exosome-Derived Genes for Constructing Diagnostic, Prognostic and Recurrence Models and Predicting Therapeutic Response for Hepatocellular Carcinoma

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