# Tumors located in the brain impair the frequency and phenotype of dendritic cells in blood and tumor

**Authors:** Bryan Gardam, Tessa Gargett, Eunwoo Nam, Sidra Khan, Rebecca J. Ormsby, Santosh I. Poonnoose, Julie M. Bracken, Anupama Pasam, Sakthi Lenin, Briony L. Gliddon, Melinda N. Tea, Chloe L. Shard, Stuart M. Pitson, Guillermo A. Gomez, Katherine A. Pillman, Shahneen Sandhu, Michael P. Brown, Lisa M. Ebert

PMC · DOI: 10.1016/j.isci.2026.115160 · iScience · 2026-02-26

## TL;DR

Brain tumors reduce the number and function of immune cells called dendritic cells in blood and tumors, and this is worsened by common treatments like corticosteroids.

## Contribution

First comprehensive characterization of dendritic cell subsets in brain tumor patients and identification of mouse models replicating these defects.

## Key findings

- Patients with brain tumors have fewer dendritic cells in blood compared to those with non-brain tumors.
- Dendritic cells are less abundant in brain tumors than in lung tumors.
- Both brain tumors and corticosteroid use are linked to dendritic cell defects.

## Abstract

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.

•Lower frequency of blood DCs in patients with brain, compared to non-brain, tumors•DCs are detectable within brain tumors, but less abundantly than in lung tumors•The presence of a brain tumor and corticosteroid use are both linked to DC defects

Lower frequency of blood DCs in patients with brain, compared to non-brain, tumors

DCs are detectable within brain tumors, but less abundantly than in lung tumors

The presence of a brain tumor and corticosteroid use are both linked to DC defects

Immunology; oncology

## Full-text entities

- **Genes:** FLT3LG (fms related receptor tyrosine kinase 3 ligand) [NCBI Gene 2323] {aka FL, FLG3L, FLT3L, IMD125}
- **Diseases:** Tumors (MESH:D009369), brain cancers (MESH:D001932), lung tumors (MESH:D008175), DC (MESH:D054221)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12997301/full.md

## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC12997301/full.md

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Source: https://tomesphere.com/paper/PMC12997301