Background: Malignant pleural effusion (MPE) is a common clinical problem in many cancers, associated with significant mortality, and current management strategies are mostly palliative. While MPE is known to promote tumour cell growth, its immunosuppressive properties are still unclear. A better understanding of the pleural space microenvironment is necessary to develop better therapies.

Methods: We used flow cytometry to measure expression of PD-L1, HLA and CD47 following culture of malignant pleural mesothelioma cells in malignant MPE fluids and non-malignant heart failure (HF) pleural fluids compared with RPMI (supplemented with 10% FBS) and human serum. We measured IL-8, EGF, and extracellular ATP in pleural fluids before and after cell culture.

Results: PD-L1 was increased in cancer cells cultured in MPE and HF fluids compared to RPMI and human serum. Moreover, exposure of CD4+ and CD8+ T cells to MPE upregulated PD-1 expression of CD4+ T cells. No differences were detected for CD47 between the different groups. MPE fluids showed elevated IL-8 which could be further increased by culture with cancer cells, along with EGF. Extracellular ATP was more prevalent in MPE relative to non-MPE fluids.

Conclusion: Our study established PD-1/PD-L1, and IL-8, as important mediators of immunosuppression in MPE, prompting a re-evaluation of clinical guidelines to adopt earlier intervention and a more targeted treatment approach.