CCL11/CCR3-dependent eosinophilia alleviates malignant pleural effusions and improves prognosis
The role of eosinophils in the development and progression of malignant pleural effusion (MPE) remains unclear. However, MPE is a frequently occurring manifestation of advanced cancer and is often associated with a poor prognosis. While current treatment options for MPE can provide palliative care, alternative therapies are urgently needed. To investigate this role, eosinophil counts were determined using flow cytometry and immunofluorescence. Eosinophil-deficient mice (Eos-null) and Cd3d -promoter Il5 transgenic (Il5 Tg) mice were subjected to a mouse model of MPE. Eosinophils were isolated by magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS), and their transcriptional profile was obtained by RNA sequencing. Finally, we evaluated the effects of the C-C motif chemokine ligand 11 (CCL11) and a C-C motif chemokine receptor 3 (CCR3) axis on MPE pathology using recombinant mouse CCL11 and a CCR3 inhibitor. In humans, eosinophil counts were increased in MPE and negatively correlated with the LENT score. In animal models, eosinophils were rapidly recruited to the pleural cavity when challenged with tumor cells. Interestingly, eosinophil deficiency worsened MPE, while an increase in eosinophils through various methods improved MPE. Furthermore, the recruitment of eosinophils may be influenced by the CCL11-CCR3 axis. Taken together, the study highlights the protective role of eosinophils against MPE formation, indicating their potential as a therapeutic strategy. Moreover, the CCL11-CCR3 axis may be a viable target for MPE treatment. Overall design: We sorted total eosinophils from the pleural lavage fluid and bone marrow of wildtype mice after the injection of LLC cells. The cells were then subjected to bulk RNA-seq indicated. Libraries were pair-end (100 bp) sequenced on a MGISEQ-500 (DNBSEQ).