Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

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Item Type:

Article

Title:

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Creators Name:

Bischoff, P. and Trinks, A. and Obermayer, B. and Pett, J.P. and Wiederspahn, J. and Uhlitz, F. and Liang, X. and Lehmann, A. and Jurmeister, P. and Elsner, A. and Dziodzio, T. and Rückert, J.C. and Neudecker, J. and Falk, C. and Beule, D. and Sers, C. and Morkel, M. and Horst, D. and Blüthgen, N. and Klauschen, F.

Abstract:

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 CP(2)E 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 N(3)MC 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.

Keywords:

Adenocarcinoma of Lung, CD8-Positive T-Lymphocytes, Gene Expression Profiling, Lung Neoplasms, Neoplastic Gene Expression Regulation, Prognosis, Single-Cell Analysis, Survival Rate, Transcriptome, Tumor Biomarkers, Tumor Microenvironment, Tumor-Infiltrating Lymphocytes

Source:

Oncogene

ISSN:

0950-9232

Publisher:

Nature Publishing Group

Volume:

Page Range:

6748–6758

Date:

16 December 2021

Official Publication: