Tumors located in the brain impair the frequency and phenotype of dendritic cells in blood and tumor
We demonstrate multiple DC defects in patients with brain tumors. This includes a profound reduction in the frequency of multiple DC subsets, diminished activation marker expression, and reduced Flt3L levels in cancer patients with brain tumors compared to those without. We also demonstrate reduced intra-tumoral DCs in brain compared to lung tumors. This is the first time DC subsets have been fully characterized in a range of brain tumor patients. Importantly, corticosteroid usage was closely associated with DC defects, highlighting the adverse effects of a standard symptomatic treatment on these critical immune cells. However, tumors located within the brain also directly contribute to DC defects. Finally, we identified several mouse brain tumor models that replicate key observations in patients and may be used to further understand this endogenous DC deficiency and to develop approaches to restore DCs, ultimately leading to new combination immunotherapies for the treatment of brain cancers.
Authors
- Melinda Nay Tea (ORCID: https://orcid.org/0000-0001-7045-1198)
- Chloé Shard (ORCID: https://orcid.org/0000-0002-7408-9269)
- Eunwoo Nam (ORCID: https://orcid.org/0000-0001-9507-1415)
- Santosh Poonnoose (ORCID: https://orcid.org/0000-0002-9486-4904)
- Stuart Maxwell Pitson (ORCID: https://orcid.org/0000-0002-9527-2740)
- Briony L. Gliddon (ORCID: https://orcid.org/0000-0003-3928-7478)
- Sakthi Lenin (ORCID: https://orcid.org/0000-0003-3054-444X)
- Shaheen Khan (ORCID: https://orcid.org/0009-0008-7691-9810)
- Katherine A. Pillman (ORCID: https://orcid.org/0000-0002-5869-889X)
- Lisa M. Ebert (ORCID: https://orcid.org/0000-0002-8041-9666)
- Bryan Gardam (ORCID: https://orcid.org/0000-0001-6612-9331)
- Rebecca J. Ormsby (ORCID: https://orcid.org/0000-0002-4256-7481)
- Anupama Pasam
- Tessa Gargett
- Julie M Bracken
- Michael P. Brown
- Shahneen Sandhu
- Guillermo A. Gomez
Institutions
- Royal Adelaide Hospital (AU)
- The University of Melbourne (AU)
- Flinders University (AU)
- Peter MacCallum Cancer Centre (AU)
- Flinders Medical Centre (AU)
- SA Health (AU)
- Centre for Cancer Biology (AU)
- The University of Adelaide (AU)
Publication Details
- Journal
- iScience
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1016/j.isci.2026.115160
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00