Correlation of levels of extracellular vesicles in peripheral and pulmonary blood plasma with pathological stages of lung cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15558-e15558
Author(s):  
Hyun Koo Kim ◽  
Byeong Hyeon Choi ◽  
Yu Hua Quan ◽  
Jiyun Rho ◽  
Sunghoi Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Human Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Peripheral Vein ◽  
Healthy Human ◽  
Lung Cancer Patients ◽  
Pathological Stages

e15558 Background: Exosome concentration is known to be higher in cancer patients than in healthy individuals. In this study, we observed that the levels of exosomes differ in tumor-draining pulmonary blood and in peripheral blood in animal models and human subjects at different pathological stages of lung cancer. Methods: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from a peripheral vein in all groups, and pulmonary blood was collected intraoperatively from all groups, except the healthy human controls. Quantitative analysis of exosomes was performed by nanoparticle tracking assay, CD63 enzyme-linked immunosorbent assay, and western blotting. Results: The peripheral blood of lung cancer-bearing animals and patients with lung cancer carried higher amounts of exosome than that from healthy controls ( p < 0.01 and p < 0.001, respectively). Moreover, pulmonary blood from lung cancer-bearing animals and patients had significantly higher exosome levels, compared to preoperative peripheral blood ( p < 0.01 and p < 0.0001, respectively). In patients, pulmonary exosome levels showed higher correlation with pathological stages of lung cancer than the peripheral exosome levels. Conclusions: Exosome levels increased with increasing grade of lung cancer, and this trend was more prominent in the pulmonary than in the peripheral blood.

scholarly journals High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2966
Author(s):  
Dagmar Riemann ◽  
Wolfgang Schütte ◽  
Steffi Turzer ◽  
Barbara Seliger ◽  
Miriam Möller
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Risk Factor ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Therapy Response ◽  
Inhibitor Therapy ◽  
Strong Positive Correlation ◽  
Blood Monocytes ◽  
Lung Cancer Patients

The aim of this study was to investigate the expression of the coinhibitory molecule PD-L1/CD274 in monocytes and dendritic cells (DC) in the blood of lung cancer patients undergoing PD1 inhibitor therapy and to correlate data with patient’s outcome. PD-L1/CD274 expression of monocytes, CD1c+ myeloid DC (mDC) and CD303+ plasmacytoid DC (pDC) was determined by flow cytometry in peripheral blood at immunotherapy onset. The predictive value of the PD-L1/CD274-expression data was determined by patients’ survival analysis. Patients with a high PD-L1/CD274 expression of monocytes and blood DC subpopulations rarely responded to PD1 inhibitor therapy. Low PD-L1/CD274 expression of monocytes and DC correlated with prolonged progression-free survival (PFS) as well as overall survival (OS). The highest PD-L1/CD274 expression was found in CD14+HLA-DR++CD16+ intermediate monocytes. Whereas the PD-L1/CD274 expression of monocytes and DC showed a strong positive correlation, only the PD-L1/CD274 expression of DC inversely correlated with DC amounts and lymphocyte counts in peripheral blood. Our results implicate that a high PD-L1/CD274 expression of blood monocytes and DC subtypes is a risk factor for therapy response and for the survival of lung cancer patients undergoing PD1 inhibitor therapy.

scholarly journals Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ryo Arai ◽  
Sayo Soda ◽  
Tomoko Okutomi ◽  
Hiroko Morita ◽  
Fumito Ohmi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Lipid Accumulation ◽  
Stage Iii ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Treatment Naïve ◽  
Anticancer Immunity

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.

scholarly journals High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients

2017 ◽  
Vol 114 (10) ◽  
pp. 2544-2549 ◽  
Author(s):  
Yin Tang ◽  
Zhuo Wang ◽  
Ziming Li ◽  
Jungwoo Kim ◽  
Yuliang Deng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Pleural Fluid ◽  
High Throughput ◽  
Targeted Therapies ◽  
Peripheral Blood ◽  
Detection Scheme ◽  
Lung Cancer Patients

Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid. We describe a highly sensitive approach for rapid detection of metabolically active tumor cells in MPE via exploiting the altered glucose metabolism of tumor cells relative to benign cells. Metabolically active tumor cells with high glucose uptake, as evaluated by a fluorescent glucose analog (2-NBDG), are identified by high-throughput fluorescence screening within a chip containing 200,000 addressable microwells and collected for malignancy confirmation via single-cell sequencing. We demonstrate the utility of this approach through analyzing MPE from a cohort of lung cancer patients. Most candidate tumor cells identified are confirmed to harbor the same driver oncogenes as their primary lesions. In some patients, emergence of secondary mutations that mediate acquired resistance to ongoing targeted therapies is also detected before resistance is manifested in the clinical imaging. The detection scheme can be extended to analyze peripheral blood samples. Our approach may serve as a valuable complement to cytology in MPE diagnosis, helping identify the driver oncogenes and resistance-leading mutations for targeted therapies.

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