Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment

Salamon, Pazit; Mekori, Yoseph A.; Shefler, Irit

doi:10.1007/s00262-019-02459-w

Cited by 28 publications

(18 citation statements)

References 30 publications

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“…Mast cells, present in strategic locations of human lung [ 19 , 20 , 26 , 32 ], are involved in several pulmonary diseases [ 22 , 31 ], lung remodeling [ 112 , 113 ], COPD [ 9 , 12 , 32 ], lung cancer [ 114 , 115 , 116 ], and asthma [ 17 , 19 ]. In recent years, the widespread use of ART has improved the survival of people with HIV [ 1 ], leading to the emergence of chronic inflammatory lung diseases as a noteworthy concern in this population [ 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

et al. 2020

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Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.

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Section: Discussionmentioning

confidence: 99%

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

et al. 2020

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“…Next, quantification (scoring) of immune-cell infiltration and immune-related pathways or functions using ssGSEA showed that the levels of mast cells and Tfh cells in the high-risk group in the training set and validation set were low, and that T-cell costimulatory pathways were inhibited. Studies have shown that mast cells exhibit weak phagocytosis and can cause lysis and destruction of tumor cells upon contact with lung cancer cells [ 22 ], and that Tfh cells (as a T-cell subset) participate in antitumor immunity [ 23 ]. In addition, activation of T-cell costimulatory pathways plays an important part in the activation of antitumor cluster of differentiation (CD)4+ T cells and CD8+ T cells [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that mast cells exhibit weak phagocytosis and can cause lysis and destruction of tumor cells upon contact with lung cancer cells [22], and that Tfh cells (as a T-cell subset) participate in antitumor immunity [23]. In addition, activation of T-cell costimulatory pathways plays an important part in the activation of antitumor cluster of differentiation (CD)4+ T cells and CD8+ T cells [24].…”

Section: Studies Have Shown That Thbs1 Has a Tumor-suppressive Role In Lung Adenocarcinoma Andmentioning

confidence: 99%

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes

et al. 2021

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We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan–Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

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“…[34] Mechanistically, it was observed that tumor-derived microvesicles from non-small-cell lung cancer (NSCLC) cells are internalized by mast cells, which enhances the migratory ability of mast cells and promotes the release of TNF-alpha and MCP-1. [35] In EC, however, there are some con icting reports about the effect of mast cell in ltration on prognosis. Tinge et al found that the number of mast cells was not related to prognosis in EC patients,[36] but Fakhrjou et al pointed out that high mast cell density in the invasive edge of the tumor correlated with tumor progression and poorer survival.…”

Section: Discussionmentioning

confidence: 99%

A Novel Potential Diagnostic and Prognostic Biomarker for Esophageal Cancer

Miao¹,

Xie²,

Xu³

et al. 2021

Preprint

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Background: Esophageal cancer (EC) is a lethal malignancy of the digestive tract with high morbidity and mortality rates, lacking molecular biomarkers for EC diagnosis and prognosis with high specificity and sensitivity.Methods: Downloaded from the Cancer Genome Atlas (TCGA), the high-throughput transcriptome sequencing mRNA data was normalized, after which dysregulated genes were identified via limma package. Weight gene coexpression network analysis (WGCNA) was performed to select diagnostic modules and candidate genes. Later, Hub genes were screened through functional enrichment, LASSO Cox regression and survival analysis. Furthermore, we performed comparation with other biomarkers and investigated the association between our target gene and immune microenvironment.Results: Esophageal adenocarcinoma subtype and esophageal squamous cell carcinoma subtype displayed similar expression patterns in terms of differentially expressed genes, which indicates the existence of consensus biomarkers. After a series of analyses, including weighted gene coexpression network analysis, Gene Ontology enrichment analysis and Cox regression analysis, CMA1 was identified as an abnormally upregulated biomarker with highest diagnostic and prognostic potential. Moreover, CMA1 might exert its effect by influencing the immune microenvironment. Conclusion: CMA1 is a potential biomarker for EC in not only diagnosis but also prognosis. Future prospective clinic trials are expected to evaluate its performance in clinical practice.

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Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment

Cited by 28 publications

References 30 publications

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes

A Novel Potential Diagnostic and Prognostic Biomarker for Esophageal Cancer

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