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http://purl.uniprot.org/citations/31953311http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31953311http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-19-2184"xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Reuss D."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"von Deimling A."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Abdollahi A."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Rapp C."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Mock A."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Martins L.R."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Herold-Mende C.C."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Debus J."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Unterberg A."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Grabe N."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Warta R."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Jungk C."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Geisenberger C."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Dettling S."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/author"Pocha K."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/pages"2231-2243"xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/title"Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival."xsd:string
http://purl.uniprot.org/citations/31953311http://purl.uniprot.org/core/volume"26"xsd:string
http://purl.uniprot.org/citations/31953311http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31953311
http://purl.uniprot.org/citations/31953311http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31953311
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