Total Protein–Chloride Ratio in Pleural Fluid Independently Predicts Overall Survival in Malignant Pleural Effusion at the First Diagnosis

ObjectivePre-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 MethodsA 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.ResultsWe 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.ConclusionIn 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.

Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion

BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.