INNV-33. Investigative needle core biopsies support multimodal deep-data generation in glioblastoma

Abstract INTRODUCTION Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Standard endpoints such as overall survival, progression free survival or radiology are coarse markers of treatment response, and there is a strong need to improve the current understanding of how the tumor, host immune system and tumor microenvironment respond to therapies. Currently, few opportunities exist to obtain additional tissue samples to understand tumor responses apart from initial surgery. This lack of visibility into tumor and immune co-evolution under treatment is a fundamental limitation in our ability to develop and advance new GBM therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. OBJECTIVE The goal of the present study was the investigate the feasibility of performing highly resolved multi-omics analyses on routine stereotactic biopsy samples obtained during surgery. METHODS Single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics was performed on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX)models RESULTS Optimized workflows resulted in sufficient yield to perform single cell RNA sequencing of biopsy samples and matched spatial proteomic profiling. MHC Class I immunopeptidomics and phosphoproteomics was generated and cross referenced to single cell gene expression data. Spatial proteomics data was integrated with single cell RNA sequencing and spatial metabolomics data. Multi-modal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. Intra- and inter-regional biopsy variance was also quantified. Finally, patient derived xenografts were generated using needle core biopsies. CONCLUSION In conclusion, investigative biopsies provide data-rich insight into disease processes and will likely play an increasingly important role in evaluating treatment responses going forward.

Authors

Institutions

Publication Details

Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.0922
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

INNV-33. Investigative needle core biopsies support multimodal deep-data generation in glioblastoma

Forest M. White, Calixto‐Hope G. Lucas, Ryuhjin Ahn, Keith Lloyd Ligon et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

INNV-33. Investigative needle core biopsies support multimodal deep-data generation in glioblastoma

Forest M. White, Calixto‐Hope G. Lucas, Ryuhjin Ahn, Keith Lloyd Ligon, Yuval Elhanati, Jennifer Gantchev, Tejus Bale, Betty Y.S. Kim, Kenny Kwok Hei Yu, Jason T. Huse, Frederick F. Lang, Stuart S. Levine, E. Antonio Chiocca, Vinay K. Puduvalli, Nathalie Y.R. Agar, Alicia D. D’Souza, Adrienne Ann Boire, Sangeeta Goswami, Gerard Baquer, Sonali Jindal, David A. Reardon, Michael J. Cima, Chetan Bettegowda, Rameen Beroukhim, Padmanee Sharma, Michael S. Regan, Sreyashi Basu, Alexei Stortchevoi, Viviane Tabar, Matthias Holdhoff, Marc Williams, Cameron Brennan, Zaki Abou-Mrad, Charles Couturier, The GBM TeamLab
article en

Abstract

Abstract INTRODUCTION Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Standard endpoints such as overall survival, progression free survival or radiology are coarse markers of treatment response, and there is a strong need to improve the current understanding of how the tumor, host immune system and tumor microenvironment respond to therapies. Currently, few opportunities exist to obtain additional tissue samples to understand tumor responses apart from initial surgery. This lack of visibility into tumor and immune co-evolution under treatment is a fundamental limitation in our ability to develop and advance new GBM therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. OBJECTIVE The goal of the present study was the investigate the feasibility of performing highly resolved multi-omics analyses on routine stereotactic biopsy samples obtained during surgery. METHODS Single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics was performed on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX)models RESULTS Optimized workflows resulted in sufficient yield to perform single cell RNA sequencing of biopsy samples and matched spatial proteomic profiling. MHC Class I immunopeptidomics and phosphoproteomics was generated and cross referenced to single cell gene expression data. Spatial proteomics data was integrated with single cell RNA sequencing and spatial metabolomics data. Multi-modal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. Intra- and inter-regional biopsy variance was also quantified. Finally, patient derived xenografts were generated using needle core biopsies. CONCLUSION In conclusion, investigative biopsies provide data-rich insight into disease processes and will likely play an increasingly important role in evaluating treatment responses going forward.

Neuro-OncologyVol. 27(Supplement_5)
Broad Institute (US), Brigham and Women's Hospital (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Johns Hopkins University (US), Johns Hopkins Medicine (US), Breakthrough (US), Dana-Farber Cancer Institute (US), Massachusetts Institute of Technology (US)
Openalex Percentile: Top 51%
Glioma Diagnosis and Treatment
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.