Change in Cytokine Profiles Released by Mast Cells Mediated by Lung Cancer-derived Exosome Activation Potentiate Cancer-associated Thrombosis

Abstract Background: Cancer-associated thrombosis is a significant cause of lung cancer mortality. Mast cells play a role in thrombosis, but their role in cancer-associated thrombosis has not been elucidated. Method: We identified the presence of mast cells in the tumor microenvironment by analysis of single-cell sequencing data. The relationship between the mast cell proportion and the expression levels of thrombosis-related genes, neutrophil-related genes, neutrophil extracellular trap-related signature genes, and immune infiltration levels in lung cancer patients was analyzed using bioinformatics. Confocal microscopic observation of bone marrow mast cell uptake after exosomes isolated from lung adenocarcinoma cell line A549 were labeled using PKH67. Mast cell degranulation detected by β-hexosaminidase release rate. Cytokine array analysis of altered mediators released by bone marrow mast cells after exosome uptake. Results:In this study, we show that the proportion of mast cells in lung cancer patients is closely related to the expression levels of thrombosis-related genes and neutrophil extracellular traps signature gene, which play a key role in thrombosis. Moreover, Lung cancer cell-derived exosomes were taken up by mast cells and activated to release procoagulant mediators. Conclusion: Our study shows that lung cancer cell-derived exosomes activate mast cells to release procoagulants, which predispose lung cancer to thrombotic complications.