A5042409986- Cancer Immunotherapy and Biomarkers
- Transplantation: Methods and Outcomes
- Cancer Genomics and Diagnostics
- Tryptophan and brain disorders
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Adenosine and Purinergic Signaling
- CAR-T cell therapy research
- Organ Transplantation Techniques and Outcomes
- Cancer Research and Treatments
- Click Chemistry and Applications
- Mechanical Circulatory Support Devices
- Polyamine Metabolism and Applications
- Veterinary Oncology Research
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Cancer, Stress, Anesthesia, and Immune Response
- Melanoma and MAPK Pathways
- Immune cells in cancer
- Histone Deacetylase Inhibitors Research
- Monoclonal and Polyclonal Antibodies Research
- Organ Donation and Transplantation
- Computational Drug Discovery Methods
- Single-cell and spatial transcriptomics
- Metabolomics and Mass Spectrometry Studies
University of Liège
2025
Roche (Switzerland)
2018-2025
Federal University of São João del-Rei
2019-2023
University Health Network
2020-2021
Toronto General Hospital
2021
Princess Margaret Cancer Centre
2021
Pierre Fabre (France)
2009-2020
University of Toronto
2020
Pontifícia Universidade Católica de Goiás
2020
Canadian Nuclear Laboratories
2019-2020
Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response inflammatory stimuli and promotes immune tolerance through effector T-cell anergy enhanced Treg function. As such, a nexus for the induction of key mechanism represents important immunotherapeutic target oncology. Starting from HTS hit 5, inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure–activity relationship...
Cold static preservation on ice (~4°C) remains the clinical standard of donor organ preservation. However, mitochondrial injury develops during prolonged storage, which limits extent time that organs can maintain viability. We explored feasibility lung storage at 10°C using a large animal model and investigated mechanisms related to protection. Functional assessments performed ex vivo perfusion demonstrated porcine lungs stored for 36 hours had lower airway pressures, higher compliances,...
Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5(+) are thought participate chemoresistance through a potential efflux function ABCB5. Nevertheless, fate these upon drugs that used in chemotherapy remains be clarified. Here we explored effect anti-melanoma treatments on cells....
Abstract Tumors use indoleamine 2,3-dioxygenase-1 (IDO1) as a major mechanism to induce an immunosuppressive microenvironment. IDO1 expression is upregulated in many cancers and considered be resistance immune checkpoint therapies. induced response inflammatory stimuli such IFNγ promotes tolerance by depleting tryptophan producing catabolites, including kynurenine, the tumor This leads effector T-cell anergy enhanced Treg function through upregulation of FoxP3. As nexus for induction key...
Background Downregulation of MHC class I expression and/or defects in the antigen presentation pathways are commonly reported human cancers. Numerous studies previously have explored extensively molecular mechanisms that underlie HLA-class and Beta2-Microglobulin (B2M) downregulation. However, techniques presently available to detect proteins lack robustness, specificity sensitivity needed for systematic integration analysis clinical trials. Furthermore, dynamics B2M not been comprehensively...
Existing survival prediction models rely only on baseline or tumor kinetics data and lack machine learning integration. We introduce a novel kinetics‐machine (kML) model that integrates markers, kinetics, four on‐treatment simple blood markers (albumin, C‐reactive protein, lactate dehydrogenase, neutrophils). Developed for immune‐checkpoint inhibition (ICI) in non‐small cell lung cancer three phase II trials (533 patients), kML was validated the two arms of III trial (ICI chemotherapy, 377...
Abstract Purpose Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. Patients methods A Phase 1b clinical trial was conducted to elucidate pharmacokinetic pharmacodynamic profiles BET inhibitor RO6870810 as...
Inhibition of NK and effector T-cell functions activation regulatory cell populations are the main immunosuppressive effects indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in immune response homeostasis, its dysregulated expression described immune-related pathologies, as tumors that hijack it to evade destruction. Thereby, inhibitors being developed stimulate antitumor responses. Existing standard quantitation methods substrate...
Recent developments in digital computational pathology support not only classical cell density based tumor characterization, but also a more comprehensive analysis of the spatial organization immune microenvironment (TiME). Leveraging that methodology current study, we tried to address question how distribution myeloid cells TiME primary colorectal cancer (CRC) affects function and location cytotoxic T cells. We applied multicolored immunohistochemistry identify monocytic (CD11b+CD14+)...
Abstract Tumors use tryptophan-catabolizing enzymes such as Indoleamine 2,3-dioxygenase-1 (IDO-1) to induce an immunosuppressive microenvironment. IDO-1 expression is upregulated in many cancers and described be a resistance mechanism immune checkpoint therapies. induced response inflammatory stimuli IFN-ã promotes tolerance through the catabolism of tryptophan accumulation catabolites including kynurenine. activity leads effector T-cell anergy enhanced Treg function upregulation FoxP3. As...
The sharing of clinical trial data and biomarker sets among the scientific community, whether originates from pharmaceutical companies or academic institutions, is critical importance to enable development new improved cancer immunotherapy modalities. Through sharing, a better understanding current therapies in terms their efficacy, safety profiles can be achieved. However, these involves number stakeholder groups including patients, researchers, private industry, journals professional...
Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding human cancer biology characterization new therapies. This work was part a comparative project assessing new, clinical-stage topoisomerase II inhibitor comparing it with etoposide in dogs spontaneous lymphoma objective to translate findings from humans. Etoposide is widely used various humans' solid hematopoietic cancer, but little data available concerning...
Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs generally accepted be the initial in a disease continuum that progresses squamous cell carcinoma (SCC), AK have treated. They also second most common reason for visits dermatologist. Several treatments available but their efficacy still needs improved. The UV-B-induced KA lesion mouse model is used preclinical studies assess of novel molecules, even though it...
Naturally occurring colorectal cancers (CRC) in rhesus macaques share many features with their human counterparts and are useful models for cancer immunotherapy; but mechanistic data lacking regarding the comparative molecular pathogenesis of these cancers.
ABSTRACT Purpose Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. Patients Methods A Phase 1b clinical trial was conducted to elucidate pharmacokinetic pharmacodynamic profiles BET inhibitor RO6870810, as...