Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma
Autor: | Christine Sers, Alexandra Trinks, Frederick Klauschen, David Horst, Annika Lehmann, Nils Blüthgen, Philipp Jurmeister, Markus Morkel, Jennifer Wiederspahn, Benedikt Obermayer, Jens Neudecker, Xizi Liang, Christine S. Falk, Jan Patrick Pett, Florian Uhlitz, Jens-Carsten Rückert, Aron Elsner, Philip Bischoff, Tomasz Dziodzio, Dieter Beule |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
Lung Neoplasms Myeloid Tumour heterogeneity Cell Adenocarcinoma of Lung CD8-Positive T-Lymphocytes Biology tumor microenvironmental patterns Article Single-cell RNA sequencing Transcriptome Lymphocytes Tumor-Infiltrating Biomarkers Tumor Tumor Microenvironment Genetics medicine Sequencing Humans Molecular Biology Tumor microenvironment Gene Expression Profiling Cancer lung adenocarcinoma Prognosis medicine.disease Gene Expression Regulation Neoplastic Survival Rate medicine.anatomical_structure Cancer cell Cancer research Adenocarcinoma Technology Platforms Single-Cell Analysis Non-small-cell lung cancer 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit CD8 |
Zdroj: | Oncogene |
ISSN: | 1476-5594 0950-9232 |
Popis: | 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. |
Databáze: | OpenAIRE |
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