A5055935755- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Autophagy in Disease and Therapy
- Genetic factors in colorectal cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Reproductive System and Pregnancy
- Genital Health and Disease
- Cervical Cancer and HPV Research
- Cancer, Lipids, and Metabolism
- Extracellular vesicles in disease
- RNA modifications and cancer
- interferon and immune responses
- Radiomics and Machine Learning in Medical Imaging
- Ovarian cancer diagnosis and treatment
VIB-KU Leuven Center for Cancer Biology
2020-2024
KU Leuven
2021-2023
VIB-KU Leuven Center for Brain & Disease Research
2023
Vlaams Instituut voor Biotechnologie
2020
Candiolo Cancer Institute
2018
New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts subtype patients based on molecular profiles have failed direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification novel TME-specific subtypes could inform new immunotherapy strategies.A refined validated cell population (MCP) counter method was applied >800 patient tumours (GBM-MCP-counter). Specifically, partition around...
The combination of atezolizumab plus bevacizumab (atezo/bev) has dramatically changed the treatment landscape advanced HCC (aHCC), achieving durable responses in some patients. Using single-cell transcriptomics, we characterize intra-tumoural and peripheral immune context patients with aHCC treated atezo/bev. Tumours from are enriched for PDL1+ CXCL10+ macrophages and, based on cell-cell interaction analysis, express high levels CXCL9/10/11 predicted to attract CXCR3+ CD8+ effector-memory T...
Glioblastoma is a highly lethal grade of astrocytoma with very low median survival. Despite extensive efforts, there still lack alternatives that might improve these prospects. We uncovered the chemotherapeutic agent temozolomide impinges on fatty acid synthesis and desaturation in newly diagnosed glioblastoma. This response is, however, blunted recurring glioblastoma from same patient. Further, we describe disrupting cellular homeostasis favor accumulation saturated acids such as palmitate...
Abstract Background Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of situ microenvironment affects clinically-predictive value this model. We implemented a GSC monolayer system investigate - vitro molecular correspondence and relationship between patient response temozolomide (TMZ). Methods DNA/RNA-sequencing was performed on 56 glioblastoma tissues 19 derived cultures. Sensitivity...
Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show autophagy ablation in TECs boosts antitumor immunity by supporting infiltration effector function of T-cells, thereby restricting melanoma growth. In melanoma-bearing mice, loss TEC leads to transcriptional expression immunostimulatory/inflammatory phenotype...
Glioblastoma (GBM) is an aggressive brain cancer that typically results in death the first 15 months after diagnosis. There have been limited advances finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤ 9 months, Short term survivors, STS) and long survival (≥ 36 Long LTS).Patients were selected from in-house cohort (GLIOTRAIN-cohort), using defined inclusion criteria (Karnofsky score > 70; age < 70 years old; Stupp...
ABSTRACT Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show autophagy ablation in TECs boosts antitumor immunity by supporting infiltration effector function of T cells, thereby restricting melanoma growth. In melanoma-bearing mice, loss TEC leads to transcriptional expression immunostimulatory/inflammatory...
ABSTRACT The present study explores the role of cytosolic branched chain amino acid aminotransferase (BCAT1) in CD8 + T cell activation, general, and tumor immunity, particular, identifies a non-canonical function protein iron homeostasis. Pharmacologic inhibition BCAT1 using novel drug ERG245 abrogates effector functions cells vitro metabolically reprograms towards increased OXPHOS. In vivo, it suppresses activation DSS colitis leading to improved disease outcomes. Remarkably, withdrawal...
Glioblastoma (GBM), a highly invasive and vascular malignancy is shown to rapidly develop resistance evolve more phenotype following bevacizumab (Bev) therapy. Rho Guanine Nucleotide Exchange Factor proteins (RhoGEFs) are mediators of key components in Bev pathways, GBM Bev-induced invasion. To identify GEFs with enhanced mRNA expression the leading edge tumours, cohort was assessed using clinical dataset. The GEF βPix/COOL-1 identified, functional effect gene depletion 3D-boyden chamber,...
Abstract Background Radiation therapy and chemotherapy using Temozolomide are the standard adjuvant treatments for patients with glioblastoma. Despite maximal treatment prognosis is still poor largely due to emergence of resistance. This resistance closely linked widely recognized inter- intra-tumoral heterogeneity in glioblastoma, although underlying mechanisms not yet fully understood. study aims investigate diverse molecular involved temozolomide Methods To induce resistance, we subjected...
<h3>Introduction/Background</h3> Non-epithelial ovarian tumours encompass a heterogeneous group of neoplasms that mainly include germ cell (GCT) and sex-cord stromal (SCST). These are characterised by an extensive inter- intratumoral heterogeneity. By applying single-cell RNA sequencing (scRNA-seq), we attempt to elucidate the complexity tumour microenvironment. <h3>Methodology</h3> We performed scRNA-seq 66 919 cells collected from 12 patients. Most fresh tissue samples were derived SCST...
Abstract Targeting HER2 with trastuzumab and lapatinib is effective in ERBB2 amplified metastatic colorectal cancer (mCRC). Although at least 30% of the patients initially respond, secondary resistance occurs most cases. Since drivers to mCRC are unknown, we exploited longitudinal plasma collections patient-derived cell models define molecular bases blockade. Levels amplification circulating tumor DNA (ctDNA) paralleled response relapse. The emergence EGFR, ERBB2, RAS, BRAF PIK3CA variants...
Abstract The tumor microenvironment (TME) shapes response to immune checkpoint blockade (ICB). Several pan-cancer single-cell RNA-sequencing (scRNA-seq) analyses have reported how TME heterogeneity profoundly differs between cancer types. These studies mainly focused on one cell type (e.g., T-cells) and combined different technologies bioinformatics pipelines with data being collected from both published newly generated datasets. A comprehensive scRNA-seq map of the involving all types is...
Abstract Glioblastoma (GBM) is an aggressive brain cancer that typically results in death the first 15 months after diagnosis. There have been limited advances finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤9 months, Short term survivors, STS) and long survival (≥36 Long LTS). Patients were selected from in-house cohort (GLIOTRAIN-cohort), using defined inclusion criteria (Karnofsky score >70; age <70 years...
Chemotherapy using temozolomide is the standard treatment for patients with glioblastoma. Despite treatment, prognosis still poor largely due to emergence of resistance. This resistance closely linked widely recognized inter- and intra-tumoral heterogeneity in glioblastoma, although underlying mechanisms are not yet fully understood. To induce resistance, we subjected 21 patient-derived glioblastoma cell cultures Temozolomide a period up 90 days. Prior cells’ molecular characteristics were...
Abstract BCAT1, the enzyme responsible for reversible transamination of leucine in cytosol, has recently been implicated development and growth various types cancer. The limited expression BCAT1 adult tissues under physiological conditions suggests that is a sensible target drug development. To better understand role cancer, we examined its gene at single cell level (scRNAseq) specimens obtained from lung, colorectal, breast, ovarian cancer patients (n=36; &gt;200,000 cells). In those...
Abstract Immune responsive gene 1 (Irg1) is an LPS-inducible within macrophages (MF) whose protein product responsible for the synthesis of itaconate from aconitate through a break in TCA cycle. Although primarily present proinflammatory macrophages, IRG1 expression has been linked with certain cancers (glioblastoma, ovarian carcinoma) and its tumor-driven upregulation peritoneal resident (pResMF) shown to contribute tumor growth. Here, we report Irg1 at single cell level (scRNAseq) samples...