Dissecting the immune landscape in pediatric high-grade glioma reveals cell state changes under therapeutic pressure
Pediatric high-grade gliomas (pHGGs) are among the most lethal childhood tumors. While therapeutic approaches were largely adapted from adult treatment regime, significant biological differences between pediatric and adult gliomas exist, which influence the immune microenvironment and may contribute to the limited response to current pHGG treatment strategies. We provide a comprehensive transcriptomic analysis of the pHGG immune landscape using single-cell RNA sequencing and spatial transcriptomics. We analyze matched malignant, myeloid, and T cells from patients with pediatric diffuse high-grade glioma (HGG) or high-grade ependymoma, examining immune microenvironment distinctions after chemo-/radiotherapy, immune checkpoint inhibition treatment, and by age. Our analysis reveals differences in the proportions of pediatric myeloid subpopulations compared to adult counterparts. Additionally, we observe significant shifts toward immune-suppressive environments following cancer therapy. Our findings offer valuable insights into potential immunotherapy targets and serve as a robust resource for understanding immune microenvironmental variations across HGG age groups and treatment regimens.
Authors
- Sanda Alexandrescu (ORCID: https://orcid.org/0000-0001-9246-4184)
- Keith L. Ligon (ORCID: https://orcid.org/0000-0002-7733-600X)
- Robert Michael Prins (ORCID: https://orcid.org/0000-0002-6282-6583)
- Ilon Liu (ORCID: https://orcid.org/0000-0002-6186-3630)
- René Geyeregger (ORCID: https://orcid.org/0000-0002-5762-790X)
- Tom B. Davidson (ORCID: https://orcid.org/0000-0002-1655-3860)
- McKenzie Shaw (ORCID: https://orcid.org/0000-0003-3734-5312)
- Gustavo Alencastro Veiga Cruzeiro (ORCID: https://orcid.org/0000-0002-0005-3984)
- Irene Slavc (ORCID: https://orcid.org/0000-0002-9419-6790)
- Maria Trissal (ORCID: https://orcid.org/0000-0003-2861-658X)
- Orr Ashenberg (ORCID: https://orcid.org/0000-0002-7802-8834)
- Sibylle Madlener (ORCID: https://orcid.org/0000-0001-7099-9997)
- Kai W. Wucherpfennig (ORCID: https://orcid.org/0000-0002-1829-302X)
- Nathan D. Mathewson (ORCID: https://orcid.org/0000-0002-8895-2609)
- Johannes Gojo (ORCID: https://orcid.org/0000-0002-8113-3416)
- Alexander Beck (ORCID: https://orcid.org/0000-0001-8641-7832)
- Natalia Stepien (ORCID: https://orcid.org/0000-0002-6658-8367)
- Daniela Loetsch
- Anže Godicelj (ORCID: https://orcid.org/0000-0002-6128-2203)
- Jenna LaBelle (ORCID: https://orcid.org/0000-0003-3843-320X)
- Sascha Marx (ORCID: https://orcid.org/0000-0002-6451-5404)
- Alicia Baumgartner (ORCID: https://orcid.org/0000-0002-0894-4167)
- Bernhard Englinger (ORCID: https://orcid.org/0000-0002-9701-2600)
- Carlos Alberto Oliveira de Biagi (ORCID: https://orcid.org/0000-0003-0700-3135)
- Hart G.W. Lidov (ORCID: https://orcid.org/0000-0002-1839-7603)
- Olivia A. Hack (ORCID: https://orcid.org/0000-0003-3962-1560)
- Andrezza Nascimento (ORCID: https://orcid.org/0000-0002-0629-7402)
- Christian Dorfer (ORCID: https://orcid.org/0000-0002-1843-7732)
- Tom Rosenberg (ORCID: https://orcid.org/0000-0002-9592-2539)
- Jayne Vogelzang (ORCID: https://orcid.org/0000-0001-8249-3600)
- Jacob S Rozowsky (ORCID: https://orcid.org/0000-0003-1101-3168)
- Lissa Baird (ORCID: https://orcid.org/0000-0001-7996-1020)
- Kee Kiat Yeo (ORCID: https://orcid.org/0000-0003-0713-6384)
- Tabitha Cooney (ORCID: https://orcid.org/0000-0002-1178-0132)
- Jason W. Pyrdol (ORCID: https://orcid.org/0000-0001-7726-4192)
- Da-Eun Jeong (ORCID: https://orcid.org/0000-0002-0186-9707)
- Sina Neyazi (ORCID: https://orcid.org/0000-0002-9861-2325)
- Christine Haberler (ORCID: https://orcid.org/0000-0003-1016-0545)
- Andreas Peyrl (ORCID: https://orcid.org/0000-0002-5736-8231)
- Lisa Mayr (ORCID: https://orcid.org/0000-0002-6841-0749)
- Jacob Haase (ORCID: https://orcid.org/0000-0003-0960-6546)
- Jiang Li (ORCID: https://orcid.org/0000-0002-9791-2553)
- Cuong Nguyen (ORCID: https://orcid.org/0000-0002-0871-5129)
- Sophia Castellani
- Rebecca D Haase
- Adrienne M Luomo
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Children's Hospital of Los Angeles (US)
- Harvard University (US)
- Heidelberg University (DE)
- Humboldt-Universität zu Berlin (DE)
- Comprehensive Cancer Center Vienna (AT)
- Parker Institute for Cancer Immunotherapy (US)
- Hopp Children's Cancer Center Heidelberg (DE)
- Dana-Farber Cancer Institute (US)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Dana-Farber Brigham Cancer Center (US)
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
- Medical University of Vienna (AT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102095
- Citations
- 5
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 8.13
Funders
- National Cancer Institute