Biology subjects

Geens, E.

Publications and source records attributed to Geens, E..

3 recordsLinked to original sources

bioRxiv2026

Longitudinal tumor ecosystem mapping defines glioblastoma treatment trajectories

Glioblastoma remains an invariably recurring and lethal brain tumor shaped by complex interactions between malignant and microenvironmental cells. How these interactions evolve under first-line standard-of-care (SOC) therapy remains unclear. We performed spatial single-cell profiling of 671 paired newly diagnosed and recurrent glioblastoma samples from 96 patients to map tumor-ecosystem evolution and its clinical relevance. We delineated five distinct patient subgroups, each characterized by unique ecosystem trajectories that correlated with clinical outcome. Patients whose tumors transitioned into oligodendrocyte-progenitor-like niches with enhanced vascular integrity, oxygenation and an IL10/CCL/MHCII immunomodulatory environment experienced improved clinical prognosis. In contrast, progression towards hypoxic mesenchymal/astrocyte-like niches dominated by strong LGALS1/SPP1/TGF{beta} immunosuppression predicted poor outcome. Furthermore, a subgroup of early-relapsing patients on SOC therapy that was characterized by a depletion of an antigen-presenting myeloid-cell-rich niche, exhibited diminished responsiveness to second-line lomustine therapy. Overall, mapping evolutions in glioblastoma ecosystems offers a novel framework for prognostic stratification and therapeutic guidance.

cancer biology↗

bioRxiv2025

Generation of a T cell receptor, cytokine and cell repertoire synovial fluid atlas to define commonalities and dissimilarities between arthritic diseases through systems immunology approaches

Although different chronic arthritic diseases are defined by clinical factors like gender, psoriasis and auto-antibodies, the biology of inflamed joints while comparing the different diseases remains neglected. Here, after curating an inflamed joint derived T-cell receptor (TCR) database, our new TRIASSIC tool identified 66303 significantly convergent TCR clonotypes. Clustering TCR clonotypes showed that synovial fluid convergence clusters (SFCCs) characterized HLA-B27+ mediated diseases (spondyloarthritis, SpA, and enthesitis-related juvenile idiopathic arthritis, JIA-ERA), Lyme arthritis and oligoarticular JIA. Single-cell transcriptomics and bulk proteomics showed upregulated interferon type I and II and TNF- pathways in oJIA. Adult and juvenile psoriatic arthritis, (JIA-)PsA, was characterized by upregulated HSP expression in monocytes and TXNIP in T-cells. We discovered an abundance of CCL5 expressing CD8+ T-cells in SF from HLA-B27+ JIA-ERA and SpA patients. JIA-ERA patients showed upregulation of CD74 and LGALS1 in Th1 and Th17 cells and IGHV7-4.1 in B-cells. oJIA patients shared a TRBV28 RG-motif on CXCL13 producing helper T-cells. Rheumatoid arthritis and (JIA-)PsA patients carried EBV-reactive cytotoxic CD8+ T-cells. Annexin signalling was shown to be important in the intercellular communication for all arthritis groups. Collectively, our work showed that chronic arthritis is characterized by both disease-specific and broadly shared mechanisms.

immunology↗

bioRxiv2022

A novel overlapping gene azyx-1 affects the translation of zyxin in C. elegans

Overlapping genes are widely prevalent, however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novel zyx-1 overlapping gene, azyx-1, with distinct regulatory functions in C. elegans. We observed conservation of alternative open reading frames overlapping the 5 region of zyxin family members in several animal species, and find shared sites of azyx-1 and zyxin proteoform expression in C. elegans. In line with a standard ribosome scanning model, our results support cis regulation of zyx-1 long isoform(s) by upstream initiating azyx-1a. Moreover, we report on a rare observation of trans regulation of zyx-1 by azyx-1, with evidence of increased ZYX-1 upon azyx-1 overexpression. Our results suggest a dual role for azyx-1 in influencing zyx-1 proteoform heterogeneity and highlights its impact on C. elegans muscular integrity and locomotion.

genetics↗