CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion

Background: Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis. Methods: Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (nÂ=Â40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student’s t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis. Results: Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (PÂ<Â0.001). In a blinded validation study, a sensitivity of 78.9Â% and a specificity of 100Â% were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (nÂ=Â140), by using a cutoff level of 3.65Â%, CD163+CD14+ cells had a sensitivity of 81.2Â% and a specificity of 100Â% for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination. Conclusions: CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.