Neutrophil dichotomy drives lymphatic metastasis
The study provides an alternative scenario in which the response of the tumor cell population itself determines the pro-tumor versus anti-tumor outcome of neutrophil-tumor interaction. Experimentally, we show that neutrophils, which were  sequentially stimulated by bacteria and tumor cell secreted factors, killed a certain proportion of tumor target cells. However, the majority of the tumor cells remained  resistant to this neutrophil-mediated killing and underwent a phenotype switch that was reminiscent of partial epithelial-to-mesenchymal transition. This phenotypic switch was associated with physical escape from NK killing and resulted in enhanced lymphatic metastasis. Overall design: Two different tumor cell lines: FaDu and H460 were treated with three different types of supernatants for 8h, 37°C, 5%CO2. Types of supernatants included: RPMI 1640 - labelled as control, derivative of neutrophils treated with supernatant from bacteria-tumor co-culture - labeled as responder (Staphylococcus Aureus) or non-responder (Streptococcus Pneumoniae or Klebsiella Pneumoniae). Each sample type comes with 3 biological replicates.