Evidence map›Paper›PMID 37061716›Full record

ArticleActa neuropathologica communications2023

Tumor lineage-specific immune response in brain metastatic disease: opportunities for targeted immunotherapy regimen?

Shiva Najjary, Johan M Kros, Willem de Koning, Disha Vadgama, Karishma Lila, Janina Wolf, Dana A M Mustafa

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Shiva NajjaryDepartment of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.ORCID 0000-0001-5088-0016
Johan M KrosDepartment of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Willem de KoningDepartment of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Disha VadgamaDepartment of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Karishma LilaDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Janina WolfDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Dana A M MustafaDepartment of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. d.mustafa@erasmusmc.nl.
Erasmus MC · NLUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastases in the brain are the most severe and devastating complication of cancer. The incidence of brain metastasis is increasing. Therefore, the need of finding specific druggable targets for brain metastasis is demanding. The aim of this study was to compare the brain (immune) response to brain metastases of the most common tumor lineages, viz., lung adenocarcinoma and breast cancer. Targeted gene expression profiles of 11 brain metastasis of lung adenocarcinoma (BM-LUAD) were compared to 11 brain metastasis of breast cancer (BCBM) using NanoString nCounter PanCancer IO 360™ Panel. The most promising results were validated spatially using the novel GeoMx™ Digital Spatial Profiler (DSP) Technology. Additionally, Immune cell profiles and expression of drug targets were validated by multiplex immunohistochemistry. We found a more active immune response in BM-LUAD as compared to BCBM. In the BM-LUAD, 138 genes were upregulated as compared to BCBM (adj. p ≤ 0.05). Conversely, in BCBM 28 genes were upregulated (adj. p ≤ 0.05). Additionally, genes related to CD45 + cells, T cells, and cytotoxic T cells showed to be expressed higher in BM-LUAD compared to BCBM (adj. p = 0.01, adj. p = 0.023, adj. p = 0.023, respectively). The spatial quantification of the immune cells using the GeoMx DSP technique revealed the significantly higher quantification of CD14 and CD163 in tumor regions of BM-LUAD as compared to BCBM. Importantly, the immune checkpoint VISTA and IDO1 were identified as highly expressed in the BM-LUAD. Multiplex immunohistochemistry confirmed the finding and showed that VISTA is expressed mainly in BM-LUAD tumor cells, CD3 + cells, and to fewer levels in some microglial cells in BM-LUAD. This is the first report on differences in the brain immune response between metastatic tumors of different lineages. We found a far more extensive infiltration of immune cells in BM-LUAD as compared to BCBM. In addition, we found higher expression of VISTA and IDO1 in BM-LUAD. Taken together, targeted immune therapy should be considered to treat patients with BM-LUAD.

Indexed as

Adenocarcinoma of LungBrain NeoplasmsBreast NeoplasmsLung NeoplasmsBrainFemaleHumansImmunotherapyPrognosisBrain metastasesBreast cancerGene expressionImmune infiltrationImmune responseLung adenocarcinoma

Identifiers

PMID37061716
PMCPMC10105417
OpenAlexW4365816757

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.