Investigate heterogeneous neutrophils in NSCLC

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We identified SiglecF+ neutrophils as a unique neutrophil subgroup in a genetically engineered mouse model of lung adenocarcinoma. SiglecF+ neutrophils are enriched in the tumor microenvironment, but their function is poorly understood. We first confirmed the existence of this group of neutrophils and then did comprehensive transcriptomic analysis. Our bioinformatic analysis predicts mitochondria disfunction and impaired neutrophil swarming in this group of neutrophils. To further understand the function of SiglecF+ neutrophils, we are generating a conditional knockout mouse model of SiglecF (SiglecF flox/flox mouse), and plan to create a mouse model specifically lacking SiglecF in neutrophils by crossing this new floxed strain to another mouse strain with neutrophil specific Cre (Catchup mice). The first batch of SiglecF flox/flox mice were born and we are in the process of characterization. To analyze how SiglecF expression is controlled, we performed RNA sequencing and identified several potential transcription factors regulating SiglecF transcription. We are exploring whether any of the candidate transcription factors are important for SiglecF expression using a mouse model in which we can specifically knock out or overexpress targets in neutrophils via CRISPR. In addition to studying heterogenous neutrophil populations in mice, we amended our clinical protocol to allow us to collect bone marrow samples and lung tumor samples from patients with lung cancers. We plan to use advanced sequencing techniques to study the heterogeneous neutrophils in bone marrow and the tumor microenvironment. We have successfully established our advanced sequencing platform and already performed the first batch of sequencing experiments.