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

Jorge Luis Galeano Niño, Hanrui Wu, Kaitlyn D. LaCourse, Andrew G. Kempchinsky, Alexander Baryiames, Brittany Barber, Neal Futran, Jeffrey Houlton, Cassie Sather, Ewa Sicinska, Alison Taylor, Samuel S. Minot, Christopher D. Johnston () and Susan Bullman ()
Additional contact information
Jorge Luis Galeano Niño: Fred Hutchinson Cancer Center
Hanrui Wu: Fred Hutchinson Cancer Center
Kaitlyn D. LaCourse: Fred Hutchinson Cancer Center
Andrew G. Kempchinsky: Fred Hutchinson Cancer Center
Alexander Baryiames: Fred Hutchinson Cancer Center
Brittany Barber: University of Washington Medical Center
Neal Futran: University of Washington Medical Center
Jeffrey Houlton: University of Washington Medical Center
Cassie Sather: Fred Hutchinson Cancer Center
Ewa Sicinska: Dana-Farber Cancer Institute
Alison Taylor: Columbia University
Samuel S. Minot: Fred Hutchinson Cancer Center
Christopher D. Johnston: Fred Hutchinson Cancer Center
Susan Bullman: Fred Hutchinson Cancer Center

Nature, 2022, vol. 611, issue 7937, 810-817

Abstract: Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types1,2. Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis1–3, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies4 and single-cell RNA sequencing5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host–microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling6, we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion–adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.

Date: 2022
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DOI: 10.1038/s41586-022-05435-0

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