ArticleNeoplasia (New York, N.Y.)2022
Spatial organization of heterogeneous immunotherapy target antigen expression in high-grade glioma.
Article in Neoplasia (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma.Cancer research · 2026Article
- Improving T-cell engager efficacy in glioblastoma with multi-antigen targeting and novel delivery approaches.Acta neuropathologica · 2026Review
- Multimodal profiling of CAR T cells against glioblastoma using a microengineered 3D tumor-on-a-chip model.Bioactive materials · 2026Article
- Review
- Article
- Mathematical modeling of combinatorial antigen targeting with multiple CAR T-cell products for glioblastoma treatment.NPJ systems biology and applications · 2026Article
- Immunologic specificity in glioblastoma: Antigen discovery and translational implications.Neuro-oncology advances · 2025Review
- Chlorotoxin-directed CAR T cell therapy for recurrent glioblastoma: Interim clinical experience demonstrating feasibility and safety.Cell reports. Medicine · 2025Article
- Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence.bioRxiv : the preprint server for biology · 2025Article
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- CAR T cell therapy for central nervous system solid tumors: current progress and future directions.Frontiers in immunology · 2025Review
- CAR-T cell therapy for the treatment of adult high-grade gliomas.NPJ precision oncology · 2024Review
- Novel tri-specific T-cell engager targeting IL-13Rα2 and EGFRvIII provides long-term survival in heterogeneous GBM challenge and promotes antitumor cytotoxicity with patient immune cells.Journal for immunotherapy of cancer · 2024Article
- Immunotherapy for Brain Tumors: Where We Have Been, and Where Do We Go From Here?Current treatment options in oncology · 2024Review
- CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.Cancers · 2023Review
- Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations.Frontiers in immunology · 2022Review
- Advancements in chimeric antigen receptor-expressing T-cell therapy for glioblastoma multiforme: Literature review and future directions.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
High-grade (WHO grades III-IV) glioma remains one of the most lethal human cancers. Adoptive transfer of tumor-targeting chimeric antigen receptor (CAR)-redirected T cells for high-grade glioma has revealed promising indications of anti-tumor activity, but objective clinical responses remain elusive for most patients. A significant challenge to effective immunotherapy is the highly heterogeneous structure of these tumors, including large variations in the magnitudes and distributions of target antigen expression, observed both within individual tumors and between patients. To obtain a more detailed understanding of immunotherapy target antigens within patient tumors, we immunochemically mapped at single cell resolution three clinically-relevant targets, IL13Rα2, HER2 and EGFR, on tumor samples drawn from a 43-patient cohort. We observed that within individual tumor samples, expression of these antigens was neither random nor uniform, but rather that they mapped into local neighborhoods - phenotypically similar cells within regions of cellular tumor - reflecting not well understood properties of tumor cells and their milieu. Notably, tumor cell neighborhoods of high antigen expression were not arranged independently within regions. For example, in cellular tumor regions, neighborhoods of high IL13Rα2 and HER2 expression appeared to be reciprocal to those of EGFR, while in areas of pseudopalisading necrosis, expression of IL13Rα2 and HER2, but not EGFR, appeared to reflect the radial organization of tumor cells around hypoxic cores. Other structural features affecting expression of immunotherapy target antigens remain to be elucidated. This structured but heterogeneous organization of antigen expression in high grade glioma is highly permissive for antigen escape, and combinatorial antigen targeting is a commonly suggested potential mitigating strategy. Deeper understanding of antigen expression within and between patient tumors will enhance optimization of combination immunotherapies, the most immediate clinical application of the observations presented here being the importance of including (wild-type) EGFR as a target antigen.
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Registered trials
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.