Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 810 - 817

Published: Nov. 16, 2022

Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe interactions. We adapted 10x Visium transcriptomics determine identity location intratumoral microbial communities patient tissues. Using GeoMx digital profiling 6 show that bacterial populate microniches are less vascularized, highly immuno‑suppressive associated with malignant cells lower levels Ki-67 as compared bacteria-negative regions. developed a RNA-sequencing method name INVADEseq (invasion–adhesion-directed expression sequencing) and, this tumours, identify cell-associated bacteria host they interact, well uncovering alterations transcriptional pathways involved inflammation, metastasis, dormancy DNA repair. Through functional studies, infected invade their surrounding environment single recruit myeloid Collectively, our data not random; instead, it organized immune epithelial functions promote progression.

Language: Английский

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Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 26, 2020

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it associated with poor treatment outcome. In mice, hematogenous F. can colonize CRC tissue using its lectin Fap2, which attaches tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as breast progresses, and occurrence of gDNA samples correlates high levels. We demonstrate Fap2-dependent binding the bacterium samples, inhibited by GalNAc. Intravascularly inoculated Fap2-expressing ATCC 23726 specifically mice mammary tumors, whereas Fap2-deficient bacteria are impaired tumor colonization. Inoculation suppresses accumulation infiltrating T cells promotes growth metastatic progression, latter two counteracted antibiotic treatment. Thus, targeting or Fap2 might beneficial during cancer.

Language: Английский

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The gut microbiota influences anticancer immunosurveillance and general health

Nature Reviews Clinical Oncology, Journal Year: 2018, Volume and Issue: 15(6), P. 382 - 396

Published: April 10, 2018

Language: Английский

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Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis

Gastroenterology, Journal Year: 2018, Volume and Issue: 156(5), P. 1440 - 1454.e2

Published: Dec. 6, 2018

Language: Английский

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Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1

EMBO Reports, Journal Year: 2019, Volume and Issue: 20(4)

Published: March 4, 2019

Language: Английский

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