Lung cancer–associated malignant pleural effusion (LC-MPE) is a defining manifestation of advanced disease and a clinically consequential pleural compartment associated with dyspnea, repeated pleural interventions, and poor outcomes. This review synthesizes current evidence across mechanisms, diagnostics, and therapeutics to reframe LC-MPE as an active pleural ecosystem rather than a passive fluid collection. We summarize how partially reversible CD8⁺ T-cell dysfunction, regulatory T-cell and macrophage programs, mesothelial/fibro-inflammatory remodeling, vascular leak with impaired drainage, and lactate- and lipid-linked metabolic reprogramming collectively sustain effusion formation, immune escape, and therapeutic resistance. We then appraise emerging diagnostic strategies according to clinical maturity. Conventional cytology and tissue confirmation remain the diagnostic backbone, whereas pleural supernatant cell-free DNA/circulating tumor DNA currently represents the most clinically mature liquid-biopsy platform; methylation assays are promising adjuncts, while extracellular vesicle-derived analytes, RNA biomarkers, multi-omics, and artificial intelligence-enabled models remain investigational. Therapeutically, drainage procedures, pleurodesis, and indwelling pleural catheters remain the foundation of care. Intrapleural PD-1 blockade and microparticle-based delivery provide early clinical proof of concept for regional pleural control, but should be viewed as adjuncts to, rather than replacements for, systemic therapy. Future progress will depend on biomarker-embedded multicenter trials, standardized pleural biospecimen and pharmacology workflows, and patient-centered endpoints. This mechanism-diagnosis-therapy continuum provides a practical framework for more precise, pleura-anchored management, with the potential to improve symptom control, reduce intervention burden, and ultimately support better patient-centered outcomes.
Cui et al. (Tue,) studied this question.