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The CXCL16/CXCR6 axis is linked to immune effector cell-associated neurotoxicity in chimeric antigen receptor (CAR) T cell therapy

GSE269379 Homo sapiens Expression profiling by high throughput sequencing; Other 10 samples Submitted 2025/05/12 Platform GPL30173
Summary
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a significant complication of CAR T-cell therapy, affecting 20% to 70% of patients. Unraveling the mechanisms underlying ICANS is crucial for improving patient outcomes. This study employed single-cell RNA sequencing (scRNA-seq) to analyze cerebrospinal fluid (CSF) cells from ICANS patients, uncovering a ICANS-specific increase in proliferating T cells compared to controls that contained both CAR and non-CAR expressing cells indicating bystander activation. These ICANS-specific proliferating T cells showed elevated expression of cytotoxic genes and the chemokine receptor gene CXCR6. Spatial transcriptomic mapping of postmortem choroid plexus and brain parenchyma of a patient with lethal ICANS revealed widespread myeloid cell infiltration and the spatial association of CXCR6+ T cells to CXCL16-expressing myeloid cells. These findings suggest that the CXCL16/CXCR6 axis may drive the recruitment of cytotoxic CAR CD4 T cells to the central nervous system during ICANS, potentially contributing to its pathogenesis and suggesting diagnostic and therapeutic potential.
Published in
The CXCL16/CXCR6 axis is linked to immune effector cell-associated neurotoxicity in chimeric antigen receptor (CAR) T cell therapy
Lu IN, Müller-Miny L, Krekeler C et al. · Genome medicine 2025 · PMID 40588764 · doi:10.1186/s13073-025-01498-6
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Direct links to NCBI, no account and no request form: the whole study as GSE269379_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 10 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1121305 and SRA study SRP512497. Searching any of these in the dataset finder brings you back here.

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10 conditions, each sampled once — no replicated groups

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