Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature.
J Immunother Cancer
; 10(7)2022 07.
Article
em En
| MEDLINE
| ID: mdl-35793869
ABSTRACT
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 ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcriptoma
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos