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Verfasst von:Pocha, Kolja [VerfasserIn]   i
 Mock, Andreas [VerfasserIn]   i
 Rapp, Carmen [VerfasserIn]   i
 Dettling, Steffen [VerfasserIn]   i
 Warta, Rolf [VerfasserIn]   i
 Geisenberger, Christoph [VerfasserIn]   i
 Jungk, Christine [VerfasserIn]   i
 Martins, Leila R. [VerfasserIn]   i
 Grabe, Niels [VerfasserIn]   i
 Reuss, David [VerfasserIn]   i
 Debus, Jürgen [VerfasserIn]   i
 Deimling, Andreas von [VerfasserIn]   i
 Abdollahi, Amir [VerfasserIn]   i
 Unterberg, Andreas [VerfasserIn]   i
 Herold-Mende, Christel [VerfasserIn]   i
Titel:Surfactant expression defines an inflamed subtype of lung adenocarcinoma brain metastases that correlates with prolonged survival
Verf.angabe:Kolja Pocha, Andreas Mock, Carmen Rapp, Steffen Dettling, Rolf Warta, Christoph Geisenberger, Christine Jungk, Leila R. Martins, Niels Grabe, David Reuss, Juergen Debus, Andreas von Deimling, Amir Abdollahi, Andreas Unterberg, Christel C. Herold-Mende
E-Jahr:2020
Jahr:May 2020
Umfang:13 S.
Fussnoten:Gesehen am 20.11.2020
Titel Quelle:Enthalten in: Clinical cancer research
Ort Quelle:Philadelphia, Pa. [u.a.] : AACR, 1995
Jahr Quelle:2020
Band/Heft Quelle:26(2020), 9, Seite 2231-2243
ISSN Quelle:1557-3265
Abstract:Purpose: To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease. - Experimental Design: Tumor-infiltrating lymphocytes (TIL) were quantified by semiautomated whole-slide analysis in brain metastases from 81 lung adenocarcinomas. Multi-color staining enabled phenotyping of TILs (CD3, CD8, and FOXP3) on a single-cell resolution. Molecular determinants of the extent of TILs in brain metastases were analyzed by transcriptomics in a subset of 63 patients. Findings in lung adenocarcinoma brain metastases were related to published multi-omic primary lung adenocarcinoma The Cancer Genome Atlas data (n = 230) and single-cell RNA-sequencing (scRNA-seq) data (n = 52,698). - Results: TIL numbers within tumor islands was an independent prognostic marker in patients with lung adenocarcinoma brain metastases. Comparative transcriptomics revealed that expression of three surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) was closely associated with TIL numbers. Their expression was not only prognostic in brain metastasis but also in primary lung adenocarcinoma. Correlation with scRNA-seq data revealed that brain metastases with high expression of surfactant genes might originate from tumor cells resembling alveolar type 2 cells. Methylome-based estimation of immune cell fractions in primary lung adenocarcinoma confirmed a positive association between lymphocyte infiltration and surfactant expression. Tumors with a high surfactant expression displayed a transcriptomic profile of an inflammatory microenvironment. - Conclusions: The expression of surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) defines an inflamed subtype of lung adenocarcinoma brain metastases characterized by high abundance of TILs in close vicinity to tumor cells, a prolonged survival, and a tumor microenvironment which might be more accessible to immunotherapeutic approaches.
DOI:doi:10.1158/1078-0432.CCR-19-2184
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1158/1078-0432.CCR-19-2184
 Volltext: https://clincancerres.aacrjournals.org/content/26/9/2231
 DOI: https://doi.org/10.1158/1078-0432.CCR-19-2184
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1740260015
Verknüpfungen:→ Zeitschrift

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