Biomedical subjects

Liat Fellus-Alyagor

Publications and source records attributed to Liat Fellus-Alyagor.

2 recordsLinked to original sources

PubMed2026

Spatial analysis reveals the evolving organization of IDH-mutant glioma.

Adult diffuse gliomas are composed of malignant cell states interwoven with the non-malignant brain microenvironment. Here, we combine spatial transcriptomics and spatial proteomics of isocitrate dehydrogenase (IDH)-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization is shaped by underlying brain anatomy. We identify a functional white-gray matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This junction is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, suggesting a role in tumor expansion. In contrast, tumors with intermediate histological features are largely disorganized, with few recurring interactions between cancer cell states and microenvironmental cell types. In high-grade tumors, hypoxia-associated structure emerges, resembling IDH-wild-type glioblastoma. Together, these findings reveal two independent axes of spatial organization-from anatomy-driven structure in low-grade tumors to hypoxia-driven organization in high-grade tumors-and establish a framework linking tumor grade to recurrent spatial interactions.

Isocitrate Dehydrogenase↗

PubMed2026

Localized PD-1 CAR T therapy reprograms neuroinflammation.

B cell-depleting therapies are effective in multiple sclerosis (MS), yet some patients relapse, underscoring the need for more precise interventions. To identify new therapeutic targets, we generated a single-cell RNA sequencing (scRNA-seq) atlas of cerebrospinal fluid (CSF), brain, and blood from non-inflammatory controls and patients with MS or other neuroinflammatory diseases. We found disease-associated enrichment of class-switched immunoglobulin G+ (IgG+) B cells and plasma cells in MS CSF. Unbiased analysis identified a rare disease-enriched subset of activated, T cell receptor (TCR)-restricted, PD-1+ T follicular helper-like cells with B cell-recruiting features. To target this population, we developed PD-1-directed chimeric antigen receptor (CAR) T cells that selectively depleted pathogenic PD-1+ CD4 T cells and locally released IL-10. This strategy attenuated central nervous system (CNS) inflammation, reprogrammed the local immune milieu, and improved clinical outcomes across murine neuroinflammation models. These findings define a CNS-localized adaptive immune circuit in MS and nominate programmable PD-1 CAR T cells as a strategy to disrupt it.

Animals↗