A5021556566- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Macrophage Migration Inhibitory Factor
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- Mesenchymal stem cell research
- Immunotherapy and Immune Responses
- Cancer Mechanisms and Therapy
- Prostate Cancer Treatment and Research
- interferon and immune responses
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Connective Tissue Growth Factor Research
- Lung Cancer Treatments and Mutations
- Xenotransplantation and immune response
- Inflammation biomarkers and pathways
- Reproductive System and Pregnancy
- Pregnancy and preeclampsia studies
- Pancreatic function and diabetes
- Bladder and Urothelial Cancer Treatments
Université de Montréal
2016-2023
Centre Hospitalier de l’Université de Montréal
2013-2023
Institute for Research in Immunology and Cancer
2018
Université Libre de Bruxelles
2018
Hospital of Prato
2018
Institut Jules Bordet
2018
Institut du Savoir Montfort
2017
The University of Melbourne
2008-2013
QIMR Berghofer Medical Research Institute
2013
Peter MacCallum Cancer Centre
2013
Extracellular adenosine is a potent immunosuppressor that accumulates during tumor growth. We performed proof-of-concept studies investigating the therapeutic potential and mechanism of action monoclonal antibody (mAb)-based therapy against CD73, an ecto-enzyme overexpressed on breast-cancer cells catalyzes dephosphorylation monophosphates into adenosine. showed anti-CD73 mAb significantly delayed primary 4T1.2 E0771 growth in immune-competent mice inhibited development spontaneous lung...
Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, investigated the relationship between and anthracycline efficacy. In TNBC patients treated anthracycline-only preoperative chemotherapy, gene was significantly lower rate of pathological complete response or disappearance invasive...
Abstract Purpose: Monoclonal antibodies (mAb) that block programmed death (PD)-1 or cytotoxic T lymphocyte antigen (CTLA-4) receptors have been associated with durable clinical responses against a variety of cancer types and hold great potential as novel therapeutics. Recent evidence suggest targeted blockade multiple immunosuppressive pathways can induce synergistic antitumor responses. Experimental Design: In this study, we investigated whether CD73, an ectonucleotidase catabolizes the...
The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that can be targeted for cancer treatment, the clinical impact of ovarian remains unclear. In this study, we investigated prognostic value high-grade serous (HGS) using gene protein expression analyses. Our results demonstrate high levels are significantly associated with shorter disease-free survival overall patients HGS cancer. Furthermore,...
CD73 is an adenosine-generating ecto-enzyme that suppresses antitumor immunity in mouse models of cancer, including prostate cancer. Although high levels are associated with poor prognosis various types the clinical impact cancer remains unclear.We evaluated prognostic value protein expression and CD8(+) cell density 285 cases on tissue microarray (TMA). Normal adjacent tumor tissues were duplicates.Univariate multivariate analyses revealed normal epithelium significantly shorter biochemical...
We have shown that CD39 and CD73 are coexpressed on the surface of murine CD4+ Foxp3+ regulatory T cells (Treg) generate extracellular adenosine, contributing to Treg immunosuppressive activity. now describe CD39, independently CD73, is expressed by a subset blood-derived human CD25+ CD127lo Treg, defined robust expression Foxp3. A further distinct population CD39+ lymphocytes can be identified, which do not express CD25 FoxP3 exhibit memory effector cellular phenotype. Differential...
CD73 is an ecto-nucleotidase overexpressed in various types of tumors that catabolizes the generation extracellular adenosine, a potent immunosuppressor. We and others have shown targeted blockade can rescue anti-tumor T cells from immunosuppressive effects adenosine. Another important function adenosine to regulate adaptive responses hypoxia. However, importance for tumor angiogenesis effect anti-CD73 therapy on remain unknown. In this study, we demonstrated expression host contribute...
Expression of the ectonucleotidase CD73 by tumor cells, stromal and immune cells is associated in cancer with suppression. In this study, we investigated role on activity anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. a prospective, randomized phase III clinical trial evaluating trastuzumab, high levels gene expression were significantly poor outcome. contrast, PD-1 PD-L1 improved immunocompetent mouse models HER2/ErbB2-driven breast cancer, host suppressed immune-mediated responses...
Abstract The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, as such, represent potential cancer targets. We investigated biological impacts of in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples experimental mouse tumors. Stromal tumoral expression significantly associated with worse survival human PDAC abolished the favorable prognostic impact presence tumor-infiltrating CD8+ T cells. In transplanted KPC tumors, both on myeloid...
Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion mice triggers obesity, non-alcoholic steatohepatitis (NASH), systemic inflammation, leading to spontaneous HCC promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine...
Abstract: We report here our experience regarding the production of double or homozygous Gal knockout (Gal KO) pigs by breeding and somatic cell nuclear transfer (SCNT). Large White × Landrace female heterozygous KO founders produced using SCNT were mated with Hampshire Duroc males to produce a F1 generation. then bred half‐sibs F2 generation which contained pigs. To determine viability mating each other, one pig was half‐sib subsequently full‐sib KO. females also males. All three types...
Ischemia-reperfusion injury (IRI) is a major limiting event for successful liver transplantation, and CD4+ T cells invariant natural killer (iNKT) have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) wildtype (WT) mouse livers were transplanted into WT recipients 18 hours storage pathological analysis was performed 6...
The formation of new lymphatic vessels, or lymphangiogenesis, is a critical step the tissue repair program. In pathological conditions involving chronic inflammation tumorigenesis, this process often dysregulated and can contribute to disease progression. Yet, lymphangiogenesis still incompletely understood. study, we identified A2a adenosinergic signaling as an important regulator inflammatory tumor-associated lymphangiogenesis. Using Adora2a (A2a)-deficient mice, demonstrated that was...
Despite the development of human epidermal growth factor receptor-2 (ErbB-2/HER2)-targeted therapies, there remains an unmet medical need for breast cancer patients with ErbB-2 overexpression. We investigated therapeutic activity agonist mAb to mouse tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (DR5) against ErbB2-driven cancer. Established tumors in BALB/c transgenic mice expressing a constitutively active ErbB-2/neuT were treated anti-DR5 and/or anti-ErbB-2 and monitored...
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In clinic, breast tumors poorly infiltrated with are more resistant to trastuzumab, patients have a worse prognosis. Because type I II IFNs critical immune-mediated mAb, we investigated effect combining polyI:C CpG trastuzumab-like therapy immunocompetent mouse models ErbB2+ cancer. We demonstrated that situ delivery combined systemic mAb triggered potent inflammatory...
Background: WNT1-Inducible Signaling Pathway Protein 1 (WISP1) is implicated in prostate cancer growth and metastasis the regulation of inflammation diverse benign diseases. The objectives this study were to assess prognostic value WISP1, its association relevance as a biomarker for immune checkpoint blockade (ICB) response.Methods: Publicly available RNA-seq datasets used evaluate WISP1 gene expression with tumor-infiltrating lymphocytes, inflamed tumor microenvironment, anti-PD-1 ICB...
Regulatory T cells (Treg) are important in mediating immune tolerance and outcomes of allotransplantation. CD4+ CD25+ CD39+ co-expression identifies memory Treg; CD25- effectors. We sought to determine CD25+/- expression from the peripheral blood patients with end stage renal failure, following transplantation during episodes acute cellular rejection.CD4+ were isolated leucocytes analysed for CD25 CD39 by flow cytometry. Treg suppressive function was measured suppression autologous effector...