Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature

Author:

Wong-Rolle, Abigail

Dong, Qiang

Zhu, Yunhua

Divakar, Prajan

Hor, Jyh Liang

Kedei, Noemi

Wong, Madeline

Tillo,Desiree

Conner, Elizabeth A

Rajan, Arun [ORCID]

Schrump, David S

Jin, Chengcheng

Germain, Ronald N

Zhao, Chen [ORCID]
Author Address

Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA., Lymphocyte Biology Section, Laboratory of Immune System Biology, NIAID, Bethesda, Maryland, USA., Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, Bethesda, Maryland, USA., NanoString Technologies Inc, Seattle, Washington State, USA., Collaborative Protein Technology Resource, NCI, Bethesda, Maryland, USA., CCR Genomics Core, National Cancer Institute, Bethesda, Maryland, USA., Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Thoracic Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA., Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA chen.zhao@nih.gov.,

Abstract:

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. 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. 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 ß-catenin was strongly correlated with bacterial burden, as were tumor histological subtypes and environmental factors. 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. NCT00242723, NCT02146170. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

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