Authors
Gardam, B., Gargett, T., Nam, E., Khan, S., Ormsby, R. J., Poonnoose, S. I., Bracken, J. M., Pasam, A., Lenin, S., Gliddon, B. L., Tea, M. N., Shard, C. L., Pitson, S. M., Gomez, G. A., Pillman, K. A., Sandhu, S., Brown, M. P., Ebert, L. M.
Abstract
Background: Professional antigen-presenting dendritic cells (DC) are critical for anti-tumor immune responses, yet patients with glioblastoma, an aggressive primary brain tumor that responds poorly to current investigational immunotherapies, appear to be deficient in DC. The extent of this deficiency, the specific DC subsets affected , and the causative mechanisms remain undefined. Furthermore, DCs in other brain tumors have not been systematically investigated. Methods: High-parameter flow cytometry was used to profile circulating and intra-tumoral DCs in patients with glioblastoma, low-grade gliomas, and brain metastases, and non-CNS cancers. Plasma DC growth factors were quantified using ELISA. We also evaluated single-cell RNA sequencing (scRNAseq) datasets to compare intra-tumoral DCs in brain and lung tumors, and quantified DC number and phenotype in three intracranial mouse brain tumor models. Results: Our studies reveal a profound systemic reduction of multiple DC subsets in the blood of patients with diverse brain tumors, coupled with reduced DC activation marker expression and lower plasma levels of FLT3L and G-CSF. Furthermore, scRNAseq analyses revealed reduced intra-tumoral DCs in glioblastoma compared to lung tumors. Circulating DC numbers inversely correlated with perioperative corticosteroid dose in patients with or without a brain tumor. However, brain tumor patients not receiving corticosteroids also had reduced DCs, suggesting a direct effect of the brain tumor. This was supported by our observation of systemic DC defects in mouse brain tumor models. Conclusions: We reveal profound DC defects in patients with brain tumors, which may contribute to current difficulties in developing effective immunotherapies for glioblastoma.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Nov 2025.
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