
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.030
vdae090.030
Final Category: Biomarkers
AcademicSubjects/MED00300
AcademicSubjects/MED00310
BMRK-09 PROGNOSTIC ROLE OF TUMOR-INFILTRATING LYMPHOCYTES AND TERTIARY LYMPHOID STRUCTURES IN BRAIN METASTASIS
Mughal Sadaf Shabbir Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Reiss Yvonne Goethe University and University Hospital Frankfurt, Institute of Neurology (Edinger-Institute), Frankfurt, Germany
Frankfurt Cancer Institute & German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany

Felsberg Jörg Institute of Neuropathology, Medical Faculty, Heinrich Heine University and University Hospital Düsseldorf, Düsseldorf, Germany

Meyer Lasse Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Macas Jadranka Goethe University and University Hospital Frankfurt, Institute of Neurology (Edinger-Institute), Frankfurt, Germany

Schlue Silja Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany

Starzetz Tatjana Goethe University and University Hospital Frankfurt, Institute of Neurology (Edinger-Institute), Frankfurt, Germany

Köhrer Karl Center for Biological and Medical Research (BMFZ), Genomics and Transcriptomics Laboratory (GTL), Heinrich Heine University, Düsseldorf, Germany

Fehm Tanja Department of Gynecology and Obstetrics, Medical Faculty, Heinrich Heine University and University Hospital Düsseldorf, Düsseldorf, Germany

Müller Volkmar Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Lamszus Katrin Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Helfrich Iris Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany
Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany

Wikman Harriet Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Berghoff Anna Department of Internal Medicine I, Clinical Division of Oncology, Medical University Vienna, Vienna, Austria

Brors Benedikt Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), Heidelberg, Germany

Plate Karlheinz Goethe University and University Hospital Frankfurt, Institute of Neurology (Edinger-Institute), Frankfurt, Germany
Frankfurt Cancer Institute & German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany

Reifenberger Guido Institute of Neuropathology, Medical Faculty, Heinrich Heine University and University Hospital Düsseldorf, Düsseldorf, Germany
German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i10i10
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Brain metastases (BrMs) constitute the most common type of brain cancer with abysmal prognosis. Given the high incidence and poor prognosis of BrM, understanding the tumor microenvironment (TME) architecture across BrM subtypes is increasingly crucial, especially with the emergence of novel immunotherapeutic agents like immune checkpoint inhibitors, which have demonstrated efficacy in melanoma and lung cancer BrM. Tertiary lymphoid structures (TLS) are spatially organized lymphoid aggregates in the TME that mediate antitumor immunity. Despite being established as prognostic and predictive markers in various cancers, their significance in BrM lacks extensive investigation. We performed gene expression profiling using paired-end RNA sequencing and multiplex immunofluorescence combined with spatial imaging on 149 human BrM samples. Cell type deconvolution analysis revealed that BrMs from non-small cell lung carcinoma (NSCLC) and malignant melanoma exhibited significantly higher immune cell infiltration compared to BrMs from breast carcinoma. Furthermore, B cell infiltration was detected in some patients, suggesting potential TLS formation. We created a metagene signature comprising TLS hallmarks in BrMs using transcriptomic profiling, allowing us to categorize BrM patients into TLS-positive and TLS-negative groups. This finding was corroborated by multiplex immunofluorescence staining of corresponding BrM tissue sections, which confirmed TLS-like aggregate formation in 40% of the BrM patients. Differential gene expression analysis highlighted the presence of activated lymphocyte-mediated immunity as well as increased immunoglobulin production signature in TLS-positive tumors. Additionally, a higher TLS signature score was associated with improved overall survival of lung carcinoma patients after BrM diagnosis. Our results underscore the heterogeneity of the tumor microenvironment in BrM, and the identification of intratumoral TLS may guide patient stratification for therapeutic interventions.
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