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| Status |
Public on Feb 27, 2024 |
| Title |
Tumor lineage-specific immune response in brain metastatic disease: opportunities for targeted immunotherapy regimen? |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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 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 less levels in some microglial cells in BM-LUAD. This is the first report on differences in the brain immune response between metastatic tumor 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.
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| Overall design |
RNA was extracted from FFPE samples of (LCBM n=11, BCBM n=11)
>>>Submitter states: RCC files will be available only upon request from the corresponding author<<<
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| Contributor(s) |
Najjary S, Kros JM, de Koning W, Vadgama D, Lila K, Wolf J, Mustafa DA |
| Citation missing |
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| Submission date |
Mar 15, 2023 |
| Last update date |
Feb 27, 2024 |
| Contact name |
Shiva Najjary |
| E-mail(s) |
s.najjary@erasmusmc.nl
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| Organization name |
Erasmus University Medical Center
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| Street address |
Dr. Molewaterplein 40
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| City |
Rotterdam |
| ZIP/Postal code |
3015 GD |
| Country |
Netherlands |
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| Platforms (1) |
| GPL32069 |
NanoString Human nCounter PanCancer IO360 Panel |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA945032 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE227427_raw_data.csv.gz |
33.5 Kb |
(ftp)(http) |
CSV |
| Processed data included within Sample table |
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