Expression of cytokines in pleural effusions and corresponding cell lines of small cell lung cancer
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ABSTRACT:
SUBMITTER: Rath B
PROVIDER: S-EPMC10891412 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionWe compared the secretome of metastatic (non-small cell lung cancer (NSCLC)) and primary (mesothelioma) malignant pleural effusions, benign effusions and the published plasma profile of patients receiving chimeric antigen receptor T cells (CAR-T), to determine factors unique to neoplasia in pleural effusion (PE) and those accompanying an efficacious peripheral anti-tumor immune response.Materials and methodsCryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytokines/chemokines using the Luminex system.ResultsProfiles of benign and malignant PE were dominated by high concentrations of sIL-6Rα, CCL2/MCP1, CXCL10/IP10, IL-6, TGFβ1, CCL22/MDC, CXCL8/IL-8 and IL-10. Malignant PE contained significantly higher (p < 0.01, Bonferroni-corrected) concentrations of MIP1β, CCL22/MDC, CX3CL1/fractalkine, IFNα2, IFNγ, VEGF, IL-1α and FGF2. When grouped by function, mesothelioma PE had lower effector cytokines than NSCLC PE. Comparing NSCLC PE and published plasma levels of CAR-T recipients, both were dominated by sIL-6Rα and IL-6 but NSCLC PE had more VEGF, FGF2 and TNFα, and less IL-2, IL-4, IL-13, IL-15, MIP1α and IFNγ.ConclusionsAn immunosuppressive, wound-healing environment characterizes both benign and malignant PE. A dampened effector response (IFNα2, IFNγ, MIP1α, TNFα and TNFβ) was detected in NSCLC PE, but not mesothelioma or benign PE. The data indicate that immune effectors are present in NSCLC PE and suggest that the IL-6/sIL-6Rα axis is a central driver of the immunosuppressive, tumor-supportive pleural environment. A combination localized antibody-based immunotherapy with or without cellular therapy may be justified in this uniformly fatal condition.
| S-EPMC6849644 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is an asbestos-related lethal malignancy refractory to conventional therapies. Since its symptoms are not specific, MPM can be easily confused with other chest diseases, especially metastatic lung adenocarcinomas (ADCA), and diagnosis is often established late when the disease is at an advanced stage. Classically, a reliable diagnosis requires histological analysis of multiple pleural biopsies. However, there is still no absolute marker for MPM. Thus, with the aim of identifying novel markers with higher specificity and sensitivity, gene expression profiling studies have been conducted using tumor specimens. Because of the cell heterogeneity of tumor samples, we decided to apply counterflow centrifugal elutriation to isolate cancer cells from pleural effusions, which are a common feature of MPM and ADCA. We profiled a total of 54 biological samples corresponding to triplicates of 13 MPM and 4 ADCA as well as the SV40-immortalized cell line MeT-5A. Our microarray results confirmed some of the existing markers which are currently used to distinguish MPM from ADCA by immunostaining of pleural biopsies and which have also been proposed for use in a PCR-based assay. Of particular interest, we also identified novel cellular markers (including predominantly COL3A1, OSAP, OCIAD2, XAGE1), which we validated by real time RT-PCR, and novel soluble markers, such as osteonectin and galectin-3, whose clinical utility as molecular targets remains to be determined. Keywords: cell type comparison three-condition experiment: ADCA vs MPM vs Met5A cells 13 MPM, 4 ADCA and Met5A were independantly grown and harvested 3 biological replicates per cell line, one replicate per array
| S-ECPF-GEOD-17310 | biostudies-other
Project description:BackgroundThe aim of the study was to assess the efficacy and side-effects of intrapleural treatment in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs).MethodsThe medical records of NSCLC patients with MPEs diagnosed in four Chinese hospitals from October 2014 to December 2019 were searched. The Kaplan-Meier method is used to calculate median overall survival (MOS) and subgroup analyses are done.ResultsA total of 285 patients were evaluated; 81.1% of patients received intrapleural treatment, and no patients received talc pleurodesis. MOS of the whole cohort was 21 months. Patients were divided into three groups: erythromycin group (EG; intrapleural treatment with drugs and erythromycin); intrathoracic treatment group (ITG; intrapleural treatment with drugs); control group (CG; no drug treatment in the pleural cavity). The MOS of patients in the EG, ITG and CG was 20, 22, and 19 months, respectively. Among patients who received only chemotherapy as systemic therapy, the MOS of intrathoracic administration group (IAG; i.e., EG and ITG) was longer than that of CG (12 vs. 6 months; p = 0.034), and the MOS of patients with a ratio of carcinoembryonic antigen in pleural effusion (PE-CEA): CEA in blood (B-CEA) ≤1 is worse than that of patients with a ratio >1 (4 vs. 12 months, p = 0.021) and that of CG (4 vs. 6 months, p = 0.442).ConclusionsIntrapleural treatment can prolong the survival of NSCLC patients with MPE who do not receive targeted treatment or who only receive chemotherapy. The PE-CEA: B-CEA ratio can be used to predict the efficacy if intrapleural treatment is indicated.
| S-EPMC8671907 | biostudies-literature
Project description:ObjectiveThis study investigated the feasibility of using malignant pleural effusion (MPE) supernatant and paired cell blocks (precipitate) for gene profiling in patients with non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS) technique.MethodsStage IV non-squamous NSCLC patients with MPE were eligible in this prospective study and recruited from Zhejiang Cancer Hospital between May 2014 and October 2015. MPE supernatant and paired precipitate sample gene alterations were determined with NGS containing 14 cancer-related genes. Progression free survival (PFS) was evaluated using Kaplan-Meier method and compared using log-rank test.ResultsA total of 102 patients were enrolled in the present study. All pleural effusions were confirmed as malignant with cytological smears. A total of 77 paired MPE supernatant and precipitate samples were acquired from the 102 patients. The results revealed that there were no statistically significant differences in the detection rate and maximum allelic fraction between supernatant and precipitate samples (P = 1.0 and P = .6). Collectively, 172 and 158 genomic alterations with 112 shared mutations were identified in supernatant and precipitate samples, respectively. Comparable PFS was found in EGFR mutation patients according to the supernatant and precipitate sample results (14.0 vs.13.9 months, P = .90).ConclusionsThese results demonstrated that MPE supernatants were comparable to precipitate samples for detection of genetic alterations. However, gene mutation heterogeneity was found between these two media types.
| S-EPMC7236047 | biostudies-literature
Project description:Non small cell lung cancer is the leading cause of cancer related mortality in the western world. RNA expression profiles have been demonstrated to be associated with a specific clinical course of the disease. We used microarray analysis to capture the whole transcriptome of a series of lung cancer cell lines to extract RNA profiles associated with specific genomic lesions Keywords: steady state Lung cancer cell lines were exponentially grown and harvested during this phase of exponential growth
| S-ECPF-GEOD-14925 | biostudies-other
Project description:BackgroundAnti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8+ T cells include less differentiated stem-like exhausted T (Texstem) cells and terminally exhausted T (Texterm) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort.MethodsPre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Texstem and Texterm CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire.ResultsHigher frequency of Texstem was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Texterm was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Texstem, median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Texstem cells also contained 'bystander' virus-specific T cells.ConclusionsThis study demonstrates that PE CD8 Texstem cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.
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Project description:Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis. However, the content of ESM-1 in pleural effusion is unclear. A retrospective study was carried out to investigate the diagnostic and prognostic values of ESM-1 with malignant pleural effusions in patients with non-small cell lung cancer (NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was calculated to assess the diagnostic value of ESM-1. Survival curves were performed by Kaplan-Meier method and survival characteristics were compared by log-rank test. Univariable and multivariate Cox proportional hazards model were carried out to analysis the significance of different prognostic factors for overall survival (OS). ESM-1 levels were significantly higher in MPE than those in BPE (p < 0.001). By ROC curve analysis, with a cutoff level of 19.58 ng/ml, the accuracy, sensitivity, and specificity for ESM-1 diagnosis MPE were 82.5%, 81.4%, and 84.0%, respectively. Moreover, NSCLC patients with pleural fluid ESM-1 levels below 19.58 ng/ml had significant longer OS than those patients with higher levels (22.09 months vs. 11.49 months, p = 0.003). Multivariate survival analysis showed that high MPE ESM-1 level was an independent prognostic factor (HR, 1.007; p = 0.039) for the OS of NSCLC patients. This study showed that ESM-1 level in pleural effusion could be a potential diagnostic and prognostic marker in NSCLC patients with MPE.
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Project description:Adenocarcinoma (AdC) is the most common lung cancer subtype and is often associated with pleural effusion (PE). Its poor prognosis is attributable to diagnostic delay and lack of effective treatments and there is a pressing need in discovering new biomarkers for early diagnosis or targeted therapies. To date, little is known about lung AdC proteome. We investigated protein expression of lung AdC in PE using the isobaric Tags for Relative and Absolute Quantification (iTRAQ) approach to identify possible novel diagnostic/prognostic biomarkers. This provided the identification of 109 of lung AdC-related proteins. We further analyzed lumican, one of the overexpressed proteins, in 88 resected lung AdCs and in 23 malignant PE cell-blocks (13 lung AdCs and 10 non-lung cancers) using immunohistochemistry. In AdC surgical samples, lumican expression was low in cancer cells, whereas it was strong and diffuse in the stroma surrounding the tumor. However, lumican expression was not associated with tumor grade, stage, and vascular/pleural invasion. None of the lung cancer cell-blocks showed lumican immunoreaction, whereas those of all the other tumors were strongly positive. Finally, immunoblotting analysis showed lumican expression in both cell lysate and conditioned medium of a fibroblast culture but not in those of A549 lung cancer cell line. PE is a valid source of information for proteomic analysis without many of the restrictions of plasma. The high lumican levels characterizing AdC PEs are probably due to its release by the fibroblasts surrounding the tumor. Despite the role of lumican in lung AdC is still elusive, it could be of diagnostic value.
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Project description:Briefly, we analyzed gene expression profiles in adherent cultures compared to sphere cultures from malignant pleural effusions (MPEs). MPEs could represent an opportunity to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas, to show that MPEs are an excellent source of tumor initiating cells for the study of lung adenocarcinoma.
| S-ECPF-MEXP-3025 | biostudies-other
Project description:Cell lines play an important role for studying tumor biology and novel therapeutic agents. We demonstrated that cell lines represent a useful and reliable in vitro system for studying basic mechanisms in lung cancer. Moreover, we presented 3 novel, comprehensively characterized SCC cell lines. Establishment and Comparative Characterization of Three Non-Small Cell Lung Cancer Cell Lines and Their Corresponding Tumor Tissue
| S-ECPF-GEOD-25251 | biostudies-other