A5031213966- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Tryptophan and brain disorders
- vaccines and immunoinformatics approaches
- Cytokine Signaling Pathways and Interactions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Pharmacological Receptor Mechanisms and Effects
- Whipple's Disease and Interleukins
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- Cancer, Stress, Anesthesia, and Immune Response
- Synthesis and biological activity
- Ubiquitin and proteasome pathways
- Gut microbiota and health
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
- Transgenic Plants and Applications
- Stress Responses and Cortisol
- Plant tissue culture and regeneration
- Renal Diseases and Glomerulopathies
- Plant Gene Expression Analysis
- Bipolar Disorder and Treatment
Ludwig Cancer Research
2011-2022
de Duve Institute
2008-2022
Walloon Excellence in Lifesciences and Biotechnology
2022
UCLouvain
2000-2019
Cliniques Universitaires Saint-Luc
2001
Institut Curie
2001
Vrije Universiteit Brussel
1986-1987
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral resistance, and IDO1 inhibition active area drug development. (TDO) unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. Here, we show enzymatically TDO expressed in a significant proportion human tumors. In preclinical model, expression tumors prevented their rejection immunized mice. We developed inhibitor,...
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates resistance signature observed human melanomas. tumors resist blockade, vaccines or adoptive T-cell therapy. recruit and activate tumor-specific CD8+ T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, are rejected...
IL-10-related T cell-derived inducible factor (IL-TIF or IL-21) is a new cytokine structurally related to IL-10 and originally identified in the mouse as gene induced by IL-9 cells mast cells. Here, we report cloning of human IL-TIF cDNA, which shares 79% amino acid identity with 25% IL-10. Recombinant was found activate signal transducer activator transcription factors-1 -3 several hepatoma cell lines. stimulation HepG2 up-regulated production acute phase reactants such serum amyloid A,...
The class II cytokine receptor family includes the receptors for IFN-alphabeta, IFN-gamma, IL-10, and IL-10-related T cell-derived inducible factor/IL-22. By screening genomic DNA databases, we identified a gene encoding protein of 231 aa, showing 33 34% amino acid identity with extracellular domains IL-22 IL-20R/cytokine 2-8, respectively, but lacking transmembrane cytoplasmic domains. A lower significant sequence was found other members this such as IL-10R (29%), 2-4/IL-10Rbeta (30%),...
Abstract Human Treg and Th clones secrete the latent form of TGF‐β, in which mature TGF‐β protein is bound to latency‐associated peptide (LAP), thereby prevented from binding receptor. We previously showed that upon TCR stimulation, human but not produce active bear LAP on their surface. Here, we show i.e. both binds glycoprotein A repetitions predominant (GARP), a transmembrane containing leucine rich repeats, present surface stimulated clones. Membrane localization mediated by GARP may be...
Vaccination of melanoma patients with tumor-specific antigens recognized by cytolytic T lymphocytes (CTL) produces significant tumor regressions in a minority patients. These appear to occur the absence massive CTL responses. To detect low-level responses, we resorted antigenic stimulation blood lymphocyte cultures limiting dilution conditions, followed tetramer analysis, cloning tetramer-positive cells, and T-cell receptor (TCR) sequence analysis clones that showed strict specificity for...
Most antigenic peptides presented by MHC class I molecules result from the degradation of intracellular proteins proteasome. In lymphoid tissues and cells exposed to IFNγ, standard proteasome is replaced immunoproteasome, in which all catalytic subunits β1, β2, β5 are their inducible counterparts β1i, β2i, β5i, have different cleavage specificities. The immunoproteasome thereby shapes repertoire peptides. existence additional forms proteasomes bearing a mixed assortment has been suggested....
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral resistance. IDO inhibition thus active area research in drug development. Recently, our group has shown that tryptophan (TDO), unrelated hepatic enzyme also catalyzing the first step degradation, expressed many tumors and this expression prevents tumor rejection locally depleting tryptophan. Herein, we report a structure-activity study on series...
A critical factor determining the effectiveness of currently used dendritic cell (DC)-based vaccines is DC activation or maturation status. We have recently shown that T-cell stimulatory capacity DCs pulsed with tumor-antigen-derived peptides can be considerably increased by activating through electroporation mRNA encoding CD40 ligand, CD70, and a constitutively active Toll-like receptor 4 (TriMix DCs). Here, we investigate whether TriMix coelectroporated whole tumor-antigen-encoding...
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from scaffold our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, most active being nanomolar potency both in enzymatic and a cellular assay, while showing no...
Indoleamine 2,3-dioxygenase (IDO) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. We have used evolutionary docking algorithm EADock to design new inhibitors this enzyme. First, we investigated modes binding all known IDO inhibitors. On basis observed docked conformations, developed a pharmacophore model, which was then devise compounds be tested inhibition. also fragment-based approach and optimize small organic...
Monoclonal antibodies that inhibit human T reg function in vivo may be used therapeutically cancer or infections.
Transforming growth factor-β1 (TGF-β1) is one of very few cytokines produced in a latent form, requiring activation to exert any its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (Tregs) suppress immune within close proximity by activating TGF-β1 presented GARP (glycoprotein A repetitions predominant) integrin αVβ8 their surface. We solved the crystal structure GARP:latent bound an antibody that stabilizes complex blocks release active TGF-β1. This finding...
Significance Immunosuppression by regulatory T cells (Tregs) is essential for the maintenance of self-tolerance, but it detrimental in cancer because Tregs inhibit antitumor immunity. Development therapeutic tools to block patients with requires a precise understanding how human suppress immune responses. We recently identified an important mechanism implicating release active form TGF-β1, potently immunosuppressive cytokine, from GARP/latent TGF-β1 complexes on surface Tregs. Here we...
The cancer-germline gene MAGE-3 codes for tumor-specific antigens recognized on many tumors by T lymphocytes. A antigen presented HLA-A1 has been used in several vaccination trials metastatic melanoma patients. Only a small minority of patients have shown evidence tumor regression. Attempts to correlate the rejections with cytotoxic lymphocyte (CTL) response against vaccine hampered low level these responses. In noncancerous individuals, frequency cell precursors MAGE-3.A1 is ≈4 × 10 -7 CD8...
Abstract We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate anti-MAGE CTL responses, we resorted to stimulation blood lymphocytes under limiting dilution conditions, followed tetramer analysis cloning tetramer-positive cells. The clones were tested their specific lytic ability TCR...