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Updated: Jun 13, 2026
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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
16.9K
A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion.
Mustafa Khasraw1, Kelly Hotchkiss1, Kenan Zhang1
1Duke University Medical Center.
Research Square
|May 2, 2025
Summary
Tumor-infiltrating lymphocyte (TIL) therapy shows promise for brain tumors. Researchers identified key genomic and spatial factors, like IL7R expression and metabolic programs, that predict successful TIL expansion for adoptive T cell therapy in glioblastoma.
Area of Science:
- Immunology
- Genomics
- Oncology
Background:
- Tumor-infiltrating lymphocyte (TIL) therapy is a promising cell-based immunotherapy recently approved for melanoma.
- Its efficacy in glioblastoma (a 'cold' tumor) is limited by poor T cell infiltration and a suppressive tumor microenvironment.
Purpose of the Study:
- To identify genomic and spatial factors influencing TIL expandability in high-grade gliomas.
- To establish a platform for selecting patients likely to benefit from TIL therapy.
Main Methods:
- Integrated multimodal profiling of high-grade gliomas, including spectral flow cytometry, TCR sequencing, single-cell RNA-seq, Xenium in situ transcriptomics, and CODEX spatial proteomics.
- Comparative analysis of TIL-generating (TIL+) versus non-generating (TIL-) tumors.
Main Results:
- Successful TIL expansion was associated with IL7R expression, perivascular immune clustering, and tumor metabolic programs (e.g., ACSS3).
- Non-expanding TIL- tumors showed enrichment for neuronal signatures, immunosuppressive transcripts (TOX, FERMT1), and tumor-associated macrophages.
Conclusions:
- This study defines critical spatial and molecular correlates for TIL manufacturing success in glioblastoma.
- A genomics-enabled selection platform is established, with prospective implementation in the GIANT clinical trial (NCT06816927) for adoptive T cell therapy.
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