Eosinophil extracellular traps formation is correlated with cancer prognosis by tumor microenvironment remodeling

The roles of eosinophil extracellular traps (EETs) in cancer have not been investigated. This research aims to unearth the association between EETs and clinical outcomes in pan-cancer. From the Cancer Genome Atlas (TCGA) program, a 28-gene EETs score was constructed. Overall, higher EETs scores indicated shorter overall survival. EETs were significantly correlated to various pro-tumor processes, including extracellular matrix remodeling, IL-17 signaling, M2 macrophage polarization, and T_reg differentiation. Immune suppressive M2 macrophages infiltrated more in the tumor microenvironment (TME), while cytotoxic cells (CD8 T and NK cells) were fewer. EETs-gene expression correlated with multiple T cell co-inhibitors. Target molecules of immune checkpoint inhibitors (ICIs) were not in proximity to the EETs disease module. Drugs against IL-5, IL-5RA, CCL-11 and IL-33 scored highly in perturbation of the disease module. Therefore, the EETs formation was coordinated with the adverse clinical outcomes and TME alternations in cancer. The role of EETs and anti-eosinophil therapy in cancer deserve further investigation in the era of immunotherapy.