Study interactions between lung microbiota and immune cells in NSCLC

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We developed a novel spatial meta-transcriptomic analysis method to generate spatially resolved information on diverse host cells and bacteria in lung tumor samples. We discovered that bacterial burden was enriched in tumor cells compared to T cells, macrophages, other immune cells, and stroma. Bacterial load increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that intratumor bacteria derive from that route of entry. Expression of oncogenic beta-catenin and epithelial-mesenchymal transition pathway genes was strongly correlated with bacterial burden, as were tumor subtypes and environmental factors. These data provide missing information on the interactions of bacteria with lung cancer cells and accompanying transcriptomic changes, providing a rationale for reducing the local intratumor microbiome for patient benefit. We have submitted our manuscript. To follow up on our findings, we are currently developing a single-cell sequencing method to capture bacterial and host transcriptional information simultaneously. In addition, we are writing a clinical trial to test the safety and feasibility of combining inhaled aztreonam and pembrolizumab in patients with NSCLC.