RT Journal Article SR Electronic 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 FD BMJ Publishing Group Ltd SP e004698 DO 10.1136/jitc-2022-004698 VO 10 IS 7 A1 Abigail Wong-Rolle A1 Qiang Dong A1 Yunhua Zhu A1 Prajan Divakar A1 Jyh Liang Hor A1 Noemi Kedei A1 Madeline Wong A1 Desiree Tillo A1 Elizabeth A Conner A1 Arun Rajan A1 David S Schrump A1 Chengcheng Jin A1 Ronald N Germain A1 Chen Zhao YR 2022 UL http://jitc.bmj.com/content/10/7/e004698.abstract AB 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.