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Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma
Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677623/ https://www.ncbi.nlm.nih.gov/pubmed/34663877 http://dx.doi.org/10.1038/s41388-021-02054-3 |
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author | Bischoff, Philip Trinks, Alexandra Obermayer, Benedikt Pett, Jan Patrick Wiederspahn, Jennifer Uhlitz, Florian Liang, Xizi Lehmann, Annika Jurmeister, Philipp Elsner, Aron Dziodzio, Tomasz Rückert, Jens-Carsten Neudecker, Jens Falk, Christine Beule, Dieter Sers, Christine Morkel, Markus Horst, David Blüthgen, Nils Klauschen, Frederick |
author_facet | Bischoff, Philip Trinks, Alexandra Obermayer, Benedikt Pett, Jan Patrick Wiederspahn, Jennifer Uhlitz, Florian Liang, Xizi Lehmann, Annika Jurmeister, Philipp Elsner, Aron Dziodzio, Tomasz Rückert, Jens-Carsten Neudecker, Jens Falk, Christine Beule, Dieter Sers, Christine Morkel, Markus Horst, David Blüthgen, Nils Klauschen, Frederick |
author_sort | Bischoff, Philip |
collection | PubMed |
description | Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues. Our analyses revealed heterogeneous carcinoma cell transcriptomes reflecting histological grade and oncogenic pathway activities, and two distinct microenvironmental patterns. The immune-activated CP²E microenvironment was composed of cancer-associated myofibroblasts, proinflammatory monocyte-derived macrophages, plasmacytoid dendritic cells and exhausted CD8+ T cells, and was prognostically unfavorable. In contrast, the inert N³MC microenvironment was characterized by normal-like myofibroblasts, non-inflammatory monocyte-derived macrophages, NK cells, myeloid dendritic cells and conventional T cells, and was associated with a favorable prognosis. Microenvironmental marker genes and signatures identified in single-cell profiles had progonostic value in bulk tumor profiles. In summary, single-cell RNA profiling of lung adenocarcinoma provides additional prognostic information based on the microenvironment, and may help to predict therapy response and to reveal possible target cell populations for future therapeutic approaches. |
format | Online Article Text |
id | pubmed-8677623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86776232021-12-29 Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma Bischoff, Philip Trinks, Alexandra Obermayer, Benedikt Pett, Jan Patrick Wiederspahn, Jennifer Uhlitz, Florian Liang, Xizi Lehmann, Annika Jurmeister, Philipp Elsner, Aron Dziodzio, Tomasz Rückert, Jens-Carsten Neudecker, Jens Falk, Christine Beule, Dieter Sers, Christine Morkel, Markus Horst, David Blüthgen, Nils Klauschen, Frederick Oncogene Article Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues. Our analyses revealed heterogeneous carcinoma cell transcriptomes reflecting histological grade and oncogenic pathway activities, and two distinct microenvironmental patterns. The immune-activated CP²E microenvironment was composed of cancer-associated myofibroblasts, proinflammatory monocyte-derived macrophages, plasmacytoid dendritic cells and exhausted CD8+ T cells, and was prognostically unfavorable. In contrast, the inert N³MC microenvironment was characterized by normal-like myofibroblasts, non-inflammatory monocyte-derived macrophages, NK cells, myeloid dendritic cells and conventional T cells, and was associated with a favorable prognosis. Microenvironmental marker genes and signatures identified in single-cell profiles had progonostic value in bulk tumor profiles. In summary, single-cell RNA profiling of lung adenocarcinoma provides additional prognostic information based on the microenvironment, and may help to predict therapy response and to reveal possible target cell populations for future therapeutic approaches. Nature Publishing Group UK 2021-10-18 2021 /pmc/articles/PMC8677623/ /pubmed/34663877 http://dx.doi.org/10.1038/s41388-021-02054-3 Text en © The Author(s) 2021 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 Bischoff, Philip Trinks, Alexandra Obermayer, Benedikt Pett, Jan Patrick Wiederspahn, Jennifer Uhlitz, Florian Liang, Xizi Lehmann, Annika Jurmeister, Philipp Elsner, Aron Dziodzio, Tomasz Rückert, Jens-Carsten Neudecker, Jens Falk, Christine Beule, Dieter Sers, Christine Morkel, Markus Horst, David Blüthgen, Nils Klauschen, Frederick Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title | Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title_full | Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title_fullStr | Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title_full_unstemmed | Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title_short | Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
title_sort | single-cell rna sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677623/ https://www.ncbi.nlm.nih.gov/pubmed/34663877 http://dx.doi.org/10.1038/s41388-021-02054-3 |
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