guest ::
| Home > Publications database > Myeloid-derived immunosuppression of chimeric antigen receptor T cells in the neuronal microenvironment of glioblastoma. |
| Home > Publications database > Myeloid-derived immunosuppression of chimeric antigen receptor T cells in the neuronal microenvironment of glioblastoma. |
| Journal Article | DKFZ-2026-00594 |
; ; ; ; ; ; ; ;
2026
BioMed Central
London
Abstract: Chimeric antigen receptor (CAR)-T cell therapy remains largely ineffective in glioblastoma (GB), where a highly immunosuppressive microenvironment and tumor heterogeneity impair therapeutic durability.Using a human neocortical brain slice model that preserves the complex GB microenvironment, we profiled interactions between natural killer group 2D (NKG2D) CAR-T cells and tumor ecosystems via PIC-seq, spatial transcriptomics, and gene regulatory network reconstruction.CAR-T cells showed an early but unsustained tumor-suppressive effect in the slice model. Single-cell profiling revealed that CAR CD8 T cells adopt an effector-skewed activation state accompanied by coordinated upregulation of checkpoint receptors and an exhaustion-associated transcription factor program. These transcriptional changes were linked to ligand-receptor signaling interactions between CAR-T cells and myeloid populations. Tumor-associated macrophages displayed enhanced phagocytic programs and spatially co-localized with mesenchymal-like GB cells within hypoxic regions. Gene regulatory network analysis identified MAF and BACH2 as candidate regulators of CD8 T cell state, with MAF enriched in CAR CD8 T cells exhibiting exhaustion-like features, and BACH2 enriched in Mock CD8 T cells consistent with less differentiated programs. In silico perturbation analyses further suggested a reciprocal effect of MAF and BACH2 on CD8 T cell transcriptional trajectories.These data map the microenvironmental and transcriptional changes associated with rapid CAR-T cell dysfunction in GB and identify candidate pathways and regulators that may be leveraged to engineer more durable cellular therapies.
Keyword(s): Brain slices ; Chimeric antigen receptor ; Glioblastoma ; Immunosuppression ; T cell exhaustion ; Transcriptional regulation
; 
; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
