TY - JOUR T1 - Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2022-004698 VL - 10 IS - 7 SP - e004698 AU - Abigail Wong-Rolle AU - Qiang Dong AU - Yunhua Zhu AU - Prajan Divakar AU - Jyh Liang Hor AU - Noemi Kedei AU - Madeline Wong AU - Desiree Tillo AU - Elizabeth A Conner AU - Arun Rajan AU - David S Schrump AU - Chengcheng Jin AU - Ronald N Germain AU - Chen Zhao Y1 - 2022/07/01 UR - http://jitc.bmj.com/content/10/7/e004698.abstract N2 - Background The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for improved prognosis and treatment.Methods To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and 3 microbe targets (bacteria, fungi, and cytomegalovirus). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in surgically resected tumor samples from 12 patients with early-stage lung cancer.Results Bacterial burden was significantly higher in tumor cells compared with T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic β-catenin was strongly correlated with bacterial burden, as were tumor histological subtypes and environmental factors.Conclusions Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer for patient benefit.Trial registration number NCT00242723, NCT02146170.Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author on request. ER -