PT  - JOURNAL ARTICLE
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
TI  - Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature
AID  - 10.1136/jitc-2022-004698
DP  - 2022 Jul 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e004698
VI  - 10
IP  - 7
4099  - http://jitc.bmj.com/content/10/7/e004698.short
4100  - http://jitc.bmj.com/content/10/7/e004698.full
SO  - J Immunother Cancer2022 Jul 01; 10
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.