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Objective: Pre-treatment biomarkers to estimate overall survival (OS) for malignant pleural effusion (MPE) are unidentified, especially those in pleural fluid. We evaluated the relationship between OS and total protein–chloride ratio in malignant pleural effusion (PE TPClR). Materials and Methods: A retrospective study was undertaken to identify patients from 2006 to 2018 who had pathologically or cytologically confirmed MPE and received no tumor-targeted therapy. We recorded the pre-treatment clinicopathologic characteristics and follow-up status. OS was estimated by the Kaplan–Meier method, and the association between variables and OS was evaluated by Cox proportional hazards models. Results: We screened 214 patients who met the eligibility criteria. The optimal cutoff value for the PE TPClR was set at 0.53. The univariate analysis showed that there was a significant correlation between PE TPClR and OS (P < 0.001). The multivariate analysis between OS and the variables selected from the univariate analysis showed that the levels of neutrophil, alkaline phosphatase, neuron-specific enolase, platelets, albumin in peripheral blood, and white blood cells in pleural effusion were also independent predictors of OS. Conclusion: In patients with MPE, pre-treatment PE TPClR independently predicts OS. Although further research is necessary to generalize our results, this information will help clinicians and patients to determine the most appropriate treatment for MPE patients. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies that leads to a poor quality of life and limits treatment options. Objective: The objective of this study was to identify biomarkers of survival in patients with MPE, which will greatly facilitate the clinical management of this complication. Methods: This retrospective study recruited patients who had been pathologically diagnosed with MPE, regardless of the type of primary cancer, at Beijing Chao-Yang Hospital over 158 months. Demographic, clinical, hematological, and pleural fluid data were collected and analyzed as potential predictors of survival, and a new predictive model was developed based on Cox and logistic regression analyses. Results: In our alternative prognostic model (n = 281), four routinely detected variables, namely, carcinoembryonic antigen (CEA) level, monocyte count, N-terminal pro B-type natriuretic peptide (NT-pro-BNP) level, and pleural effusion chloride level on admission, were identified as predictors (the CONCH prognostic score). Patients were divided into three prognosis subgroups based on risk stratification, with median survival periods of 17, 11, and 5 months, respectively. In comparison with the low-risk group, patients in the medium- and high-risk groups showed significantly poorer survival (medium-risk group: hazard ratio [HR], 1.586; 95% confidence interval [CI], 1.047– 2.402; P = 0.029; high-risk group: HR, 4.389; 95% CI, 2.432– 7.921; P < 0.001). Conclusion: Four routinely detected variables were used to develop the CONCH scoring system, which was confirmed to be an accurate prognostic score for patients with MPE. This system can guide the selection of interventions and management for MPE. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) is a frequent complication of malignancies and poses a clinical problem. CD4+ T lymphocytes are the most frequent cell population in MPE. Traditionally, CD4+ T cells are classified into two subsets based on cytokine production profiles, type 1 (Th1) and type 2 (Th2) helper T cells, which exhibit distinct functions. Recently, other T-cell subsets have been added to the Th-cell "portfolio", including regulatory T, Th17, Th9, and Th22 cells. The current review focuses on summarizing the Th-cell phenotypic characteristics, mechanism of Th-cell differentiation, and their pleural space recruitment, based on recent research. We also describe the interplay in MPE among different Th cells, as well as Th cells and lung cancer cells or mesothelial cells. Future research should expand the landscape map of human MPE immune cells, explore the immuno-regulation of B cells, and investigate the communication between macrophages and Th cells in MPE, which may facilitate meaningful advancements in the diagnoses and therapeutics of MPE. [ABSTRACT FROM AUTHOR]

IL‐10, produced by a wide variety of cells, is a highly pleiotropic cytokine that plays a critical role in the control of immune responses. However, its regulatory activity in tumor immunity remains poorly understood. In this study, we report that IL‐10 deficiency robustly suppressed the formation of malignant pleural effusion (MPE) and significantly enhanced miR‐7116‐5p expression in pleural CD4+ T cells. We demonstrated that miR‐7116‐5p suppressed IL‐10‐mediated MPE formation by inhibiting pleural vascular permeability as well as tumor angiogenesis and tumor growth. IL‐10 promoted MPE formation by suppressing miR‐7116‐5p that enhances TH1 response. We identified G protein‐coupled receptor 55 (GPR55) as a potential target of miR‐7116‐5p, and miR‐7116‐5p promoted TH1 cell function by downregulating GPR55. Moreover, GPR55 promoted MPE formation by inhibiting TH1 cell expansion through the ERK phosphorylation pathway. These results uncover an IL‐10‐mediated pathway controlling TH1 cells and demonstrate a central role for miR‐7116‐5p/GPR55/ERK signaling in the physiological regulation of IL‐10‐driven pro‐malignant responses. [ABSTRACT FROM AUTHOR]

Background: The objective of our study was to analyze the prognostic value of the combination of serum ALP and pleural effusion LDH (AL score) for malignant pleural effusion (MPE) patients. Methods: This study includes retrospective, descriptive and observational research from 1 June 2006 to 1 December 2017, which aimed to identify prognostic factors related to MPE patients. We analyzed the association of various clinical features, routinely tested markers from peripheral blood and MPE at diagnosis and overall survival (OS). All MPE patients were assigned to three groups according to their AL score. The impact of the AL score and other prognostic factors were evaluated with multivariable regression. Results: According to their AL score, 193 patients were assigned to three groups with 25 in group 0 (sALP < 65 U/L and pLDH < 155 U/L), 121 in group 1 (sALP > 65 U/L or pLDH > 155 U/L) and 47 (sALP > 65 U/L and pLDH > 155 U/L) in group 2. For groups 0, 1 and 2, median survival times (MST) were 23, 15 and 7 months, respectively. Among the three groups, MST, serum albumin level, C reactive protein, erythrocyte sedimentation rate, the ratios of platelet‐to‐lymphocyte, neutrophil‐to‐lymphocyte showed significant differences. The counts of neutrophils, monocytes, platelets and AL score (0 vs. 1, P = 0.038, hazard ratio [HR]: 1.858, 95% confidence interval [CI]: [1.034, 3.339]; 0 vs. 2, P = 0.001, HR: 2.993, 95% CI: [1.556, 5.531]) were independent prognostic indicators for OS of MPE patients. Conclusion: AL score is a promising indicator which can be used to predict the prognosis of MPE patients. It can assist physicians in the selection of patients for appropriate palliative treatment. Key points: To our knowledge, this paper is the first study that combined two enzymes (sALP and pLDH) from serum and pleural effusion and studied the prognostic value for MPE patients. It has been proved to be a promising indicator to assist physicians select patients for appropriate palliative treatment. [ABSTRACT FROM AUTHOR]

The role of IL‐10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL‐10 was a significant predictor of increased risk of death. We noted that TH1‐ and TH17‐cell content in MPE was higher in IL‐10–/– mice than in WT mice, and IL‐10 deficiency promoted differentiation into TH1 but not into TH17 cells. A higher fraction of TH1 and TH17 cells in the MPE of IL‐10–/– mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of TH1 and TH17 cells into the MPE, and IFN‐γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10‐deficient tumor cells led to decreased TH1‐ and TH17‐cell content in MPE, increased MPE volume, and reduced survival of MPE‐bearing mice. Taken together, we demonstrated that IL‐10 deficiency promoted T‐cell differentiation into TH1 cells and upregulated the CXCR3‐CXCL10 signaling pathway that recruits TH1 and TH17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice‐bearing MPE. IL‐10 promoted the development of malignant pleural effusion by suppressing the differentiation of naïve CD4+ T cells into TH1 cells and by suppressing the CXCR3‐CXCL10 signal that traffics TH1 and TH17 cells into the pleural space. [ABSTRACT FROM AUTHOR]