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Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer
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 the spatial distribution and localized effect of the microbiota withi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684076/ https://www.ncbi.nlm.nih.gov/pubmed/36385528 http://dx.doi.org/10.1038/s41586-022-05435-0 |
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author | Galeano Niño, Jorge Luis Wu, Hanrui LaCourse, Kaitlyn D. Kempchinsky, Andrew G. Baryiames, Alexander Barber, Brittany Futran, Neal Houlton, Jeffrey Sather, Cassie Sicinska, Ewa Taylor, Alison Minot, Samuel S. Johnston, Christopher D. Bullman, Susan |
author_facet | Galeano Niño, Jorge Luis Wu, Hanrui LaCourse, Kaitlyn D. Kempchinsky, Andrew G. Baryiames, Alexander Barber, Brittany Futran, Neal Houlton, Jeffrey Sather, Cassie Sicinska, Ewa Taylor, Alison Minot, Samuel S. Johnston, Christopher D. Bullman, Susan |
author_sort | Galeano Niño, Jorge Luis |
collection | PubMed |
description | 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 the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies(4) and single-cell RNA sequencing(5) 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 profiling(6), 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. |
format | Online Article Text |
id | pubmed-9684076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96840762022-11-25 Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer Galeano Niño, Jorge Luis Wu, Hanrui LaCourse, Kaitlyn D. Kempchinsky, Andrew G. Baryiames, Alexander Barber, Brittany Futran, Neal Houlton, Jeffrey Sather, Cassie Sicinska, Ewa Taylor, Alison Minot, Samuel S. Johnston, Christopher D. Bullman, Susan Nature Article 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 the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies(4) and single-cell RNA sequencing(5) 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 profiling(6), 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. Nature Publishing Group UK 2022-11-16 2022 /pmc/articles/PMC9684076/ /pubmed/36385528 http://dx.doi.org/10.1038/s41586-022-05435-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Galeano Niño, Jorge Luis Wu, Hanrui LaCourse, Kaitlyn D. Kempchinsky, Andrew G. Baryiames, Alexander Barber, Brittany Futran, Neal Houlton, Jeffrey Sather, Cassie Sicinska, Ewa Taylor, Alison Minot, Samuel S. Johnston, Christopher D. Bullman, Susan Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title | Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title_full | Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title_fullStr | Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title_full_unstemmed | Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title_short | Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
title_sort | effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684076/ https://www.ncbi.nlm.nih.gov/pubmed/36385528 http://dx.doi.org/10.1038/s41586-022-05435-0 |
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