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Key takeaways
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Patients with pediatric low-grade gliomas (pLGG) experience notable morbidity despite favorable survival outcomes.
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Our neuro-oncology researchers sought to better understand the complex interplay between tumor and immune cells within the pLGG tumor microenvironment (TME).
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The team used a multi-pronged approach of single-cell RNA sequencing, spatial transcriptomics and cytokine analysis.
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Study findings demonstrated the complexity of the pLGG TME and differences in genetic subtypes that could impact how these tumors respond to immunotherapy.
Research study background
Researchers in the Neuro-Oncology Program at Children’s Hospital Colorado have published a pre-print of a study that offers new insights into the biology of the most common pediatric brain tumors. Pediatric low-grade gliomas (pLGG) are typically managed by surgical resection, but some patients may require chemotherapy and radiation. While these pLGG tumors have an encouraging survival rate, these patients face a significant risk of recurrence and/or treatment-related complications.
“Many patients require multiple rounds of therapies over several years — some of whom I’ve treated since they were toddlers and are now entering high school — and are left with lifelong neurologic deficits, learning issues, and numerous side effects from treatment.”
- JEAN MULCAHY-LEVY, MD
In this study, investigators examined the diversity of tumor and immune cells in pLGG, the first step towards developing safer and more effective therapies for these vulnerable patients. They used a three-pronged approach to examine 23 samples from patients with pLGG who underwent tumor resection between 2011 and 2019 at Children’s Colorado. Single cell RNA sequencing identified tumor and immune cells within the tumor microenvironment (TME) and a cellular architecture among tumor cells that includes progenitor and mature cells. Immune cells included myeloid and lymphocytic cells and there were notable differences in the immune cells of two common subtypes of pLGG: pilocytic astrocytoma (PA) and ganglioglioma (GG). Cytokine analysis measured signaling molecules and showed distinct immune activity patterns between PA and GG. Among the subtypes, researchers observed a difference in the immune phenotype: KIAA1549-BRAF fusion PA tumor samples appeared to trigger more immune responses compared to BRAF V600E GG samples. Spatial transcriptomics revealed that these immune-related genes were expressed in specific areas within the TME.
Relevance to future research
This multifaceted analysis highlighted the complexity of pLGG and differences in genetic subtypes that may impact how these tumors respond to immunotherapy. The paper was recently submitted to an academic journal for peer review and potential publication.
Further research into immune cell involvement and tumor-immune interactions will be needed to validate these findings and potentially aid the development of safer, more effective therapies for pLGG.
Featured researchers
Jean Mulcahy Levy, MD
Pediatric neuro-oncologist
Center for Cancer and Blood Disorders
Children's Hospital Colorado
Associate professor
Pediatric Hematology/Oncology and Bone Marrow Transplantation
University of Colorado School of Medicine
