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

10.1093/noajnl/vdae090.005
vdae090.005
Final Category: Basic Science Brain Metastases
AcademicSubjects/MED00300
AcademicSubjects/MED00310
BSBM-06 SINGLE-CELL SPATIAL ANALYSIS OF METASTATIC BRAIN TUMORS REVEALS INTRACELLULAR BACTERIAL SIGNAL AND THEIR CORRELATION WITH THE TUMOR MICROENVIRONMENT
Morad Golnaz The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Damani Ashish The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Melendez Brenda The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Singh Bharat The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Wong Matthew The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Sahasrabhojane Pranoti The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Hoballah Yasmine The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Veguilla Fabiana The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Losh Jillian The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Ajami Nadim The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Ferguson Sherise The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Wargo Jennifer The University of Texas MD Anderson Cancer Center, Houston, TX, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i2i2
© 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

Metastatic brain tumors are associated with significant morbidity and mortality. Recent trials have demonstrated the potential efficacy of immunotherapy for the management of brain metastasis (BrM), albeit in only a subset of patients. Understanding the BrM microenvironment and identifying the factors that shape this complex milieu can facilitate optimizing treatment strategies for this disease. The microbiome has been recognized as a hallmark of cancer with a major role in shaping response to immunotherapy. However, the role of the microbiome in BrM is largely unknown. We have previously reported that bacterial signals can be detected in BrM tumors via metagenomic analyses and staining. Here we present the spatial correlation between the intra-tumoral bacterial signal and the transcriptional changes in the tumor microenvironment. Tissue digital spatial profiling (DSP) and single-cell DSP were conducted on BrM tissue microarrays using the NanoString GeoMx® and CosMx® platforms, respectively. These assays incorporated a custom panel of pan-bacterial 16S rRNA probes, enabling a comparison between tumor regions and cells that showed a positive signal for bacterial 16S rRNA versus those that did not. DSP of BrM tumors revealed anti-bacterial responses and enrichment of innate immune activity in areas with 16S signal, suggesting an active host response to intra-tumoral 16S signals. Furthermore, single-cell DSP demonstrated a heterogenous distribution of cell types harboring the 16S signal in the tumor microenvironment. In tumor cells, intracellular 16S signal was associated with an upregulation of transcripts related to neuroinflammation, chemokine, and interleukin signaling. Furthermore, immune transcriptional changes were identified in the immediate neighborhood of 16S-positive cells. Overall, this study introduces bacterial signals as a novel element within metastatic brain tumors and demonstrates their association with anti-bacterial responses and immune activity. These findings set the foundation for future mechanistic and translational studies to evaluate microbiome modulation strategies in enhancing care for brain metastasis.
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