The biological functions and clinical applications of exosomes in lung cancer

Chen, Rui; Xu, Xin; Qian, Zhiliang; Zhang, Congcong; Niu, Yongjie; Wang, Zhixian; Sun, Junhao; Zhang, Xiao; Yu, Yongchun

doi:10.1007/s00018-019-03233-y

Cited by 82 publications

(62 citation statements)

References 178 publications

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“…Exosomes are extracellular vesicles secreted by various cells (including cancer cells), and contain DNA, RNA, and proteins (104). A study evaluated the PD-L1 mRNA expression in circulating exosomes to monitor the response to PD-1-targeting antibodies in patients with melanoma or NSCLC.…”

Section: Exosomesmentioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Zhang

Pang

et al. 2020

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have brought impressive clinical benefits in a variety of malignancies over the past years, which dramatically revolutionized the cancer treatment paradigm. Monotherapy or in combination with chemotherapy of ICIs targeting programmed death 1/programmed death ligand 1 (PD-L1) has emerged as an alternative treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, constrained by primary or acquired resistance, most patients obtain limited benefits from ICIs and occasionally suffer from severe immune-related adverse events. Moreover, owing to the complexity of the tumor microenvironment and the technical limitations, clinical application of PD-L1 and tumor mutation burden as biomarkers shows many deficiencies. Thus, additional predictive biomarkers are required to further advance the precision of proper patient selection, avoiding the exposure of potential nonresponders to unnecessary immunotoxicity. Nowadays, an increasing number of investigations are focusing on peripheral blood as a noninvasive alternative to tissue biopsy in predicting and monitoring treatment outcomes. Herein, we summarize the emerging blood-based biomarkers that could predict the clinical response to checkpoint immunotherapy, specifically in patients with NSCLC.

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Section: Exosomesmentioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Zhang

Pang

et al. 2020

Front. Immunol.

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“…Furthermore, recent works have depicted their role as next-generation biomarkers based on their feasibility as therapeutic drug-delivery nanocarriers. In immunotherapy, they have generated much excitement as candidates for diagnostics and therapeutics in an array of diseases [24][25][26][27][28]. In this current study, we performed ultrastructural characterization of BDEV, their biogenesis, and identification of signatures using quantitative mass spectrometry-based proteomics from male and female Sprague Dawley rats following either long-term nicotine or saline self-administration.…”

Section: Introductionmentioning

confidence: 99%

Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

Koul

Schaal

Chand

et al. 2020

Cells

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Smoking remains a significant health and economic concern in the United States. Furthermore, the emerging pattern of nicotine intake between sexes further adds a layer of complexity. Nicotine is a potent psychostimulant with a high addiction liability that can significantly alter brain function. However, the neurobiological mechanisms underlying nicotine’s impact on brain function and behavior remain unclear. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation. To fill in this critical knowledge gap, our current study focused on identifying sex-specific brain-derived extracellular vesicles (BDEV) signatures in male and female rats post nicotine self-administration. Extracellular vesicles (EVs) are comprised of phospholipid nanovesicles such as apoptotic bodies, microvesicles (MVs), and exosomes based on their origin or size. EVs are garnering significant attention as molecules involved in cell–cell communication and thus regulating the pathophysiology of several diseases. Interestingly, females post nicotine self-administration, showed larger BDEV sizes, along with impaired EV biogenesis compared to males. Next, using quantitative mass spectrometry-based proteomics, we identified BDEV signatures, including distinct molecular pathways, impacted between males and females. In summary, this study has identified sex-specific changes in BDEV biogenesis, protein cargo signatures, and molecular pathways associated with long-term nicotine self-administration.

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“…Lung cancer is divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). As the most common subtype of NSCLC (2), lung adenocarcinoma (LUAD) has complex carcinogenic mechanisms and obvious tumor heterogeneity. Due to the continuous improvement in the diagnosis and treatment of LUAD in recent years, especially the rise of immunotherapy, the prognosis of patients has improved significantly.…”

Section: Introductionmentioning

confidence: 99%

A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma

Song

Guo

et al. 2020

Front. Oncol.

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The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to well-interpret the prognosis of patients. Using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA) database, we constructed an immune signature based on a multivariate Cox analysis (stepwise model). We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients according to the pRRophetic algorithm. Gene-set variation analysis (GSVA) was used to reveal pathway enrichment between groups. Moreover, immune microenvironment landscape was described by single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT and systematically correlated with genomic of these patients. A prognostic nomogram combining the immune signature and TNM stage to predict the prognosis was developed by multivariate Cox regression. The novel signature with four immune-related genes (MAL, MS4A1, OAS1, and WFDC2) had good robustness, which can accurately distinguish between high-and low-risk patients. Compared with low-risk patients, high-risk patients with a worse prognosis (5-year OS: 46.5 vs. 59.4%, p = 0.002) could benefit more from immunotherapy and the application of common chemotherapeutic agents such as cisplatin and paclitaxel (Wilcoxon test, all p < 0.05). There were significant differences in tumor immune microenvironment and metabolic pathways between the two groups. Additionally, the constructed nomogram had reliable predictive performance with the C-index of 0.725 (95% CI = 0.668-0.781) in the development set (n = 500), 0.793 (95% CI = 0.728-0.858) in the internal validation set (n = 250) and 0.679 (95% CI = 0.644-0.714) in the external validation set (n = 442). The corresponding calibration curves also showed good consistency. To sum up, we developed an immune-related gene signature and comprehensively evaluated LUAD immune landscape and metabolic pathways. Effective differentiation of high-and low-risk patients and accurate construction of nomogram would be helpful to the development of individualized treatment strategies.

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The biological functions and clinical applications of exosomes in lung cancer

Cited by 82 publications

References 178 publications

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma

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