ZEB1 defines suppressive neutrophils and neutrophil extracellular traps in non-small cell lung cancer.

The study aims to investigate the role of neutrophil subtypes, particularly ZEB1-positive neutrophils and their ability to form neutrophil extracellular traps (NETs), in modulating the immune microenvironment of non-small cell lung cancer (NSCLC). Despite the advent of immune checkpoint inhibitors (ICIs), a significant proportion of patients shows primary resistance, often associated with elevated neutrophil levels. Preliminary data suggest that ZEB1 may contribute to the immunosuppressive functions of neutrophils and to the formation of NETs that interfere with immune activation. The project includes the phenotypic and functional characterization of ZEB1+ neutrophils in patients undergoing ICI treatment and the analysis of their impact on immune system cells. In addition, the potential role of NETs in promoting the differentiation of hematopoietic progenitors toward immunosuppressive phenotypes is being explored. The expected outcomes may lead to the identification of novel resistance biomarkers and improve patient selection for immunotherapy.