A5047414830- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Macrophage Migration Inhibitory Factor
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- CAR-T cell therapy research
- Gastroesophageal reflux and treatments
- Brain Metastases and Treatment
- Mesenchymal stem cell research
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cancer, Stress, Anesthesia, and Immune Response
- Phagocytosis and Immune Regulation
- Cytomegalovirus and herpesvirus research
- Advanced Breast Cancer Therapies
- Neurological Complications and Syndromes
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
Université de Montréal
2016-2025
Centre Hospitalier de l’Université de Montréal
2016-2025
Pharmac
2014-2023
Georgia Southern University
2019-2021
McGill University
2001-2019
Université Libre de Bruxelles
2018-2019
Institut Jules Bordet
2018-2019
Princess Margaret Cancer Centre
2018
McGill University Health Centre
2018
Hospital of Prato
2018
Several species of intestinal bacteria have been associated with enhanced efficacy checkpoint blockade immunotherapy, but the underlying mechanisms by which microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly immune inhibitors in four mouse models cancer. We found that B. pseudolongum modulated immunotherapy response through production metabolite...
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...
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism action not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, relative contribution lymphocyte-mediated cellular cytotoxicity and antitumor cytokines remains unknown. We report here anti–ErbB-2 mAb therapy is...
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...
CD73 is a cell-surface enzyme that suppresses immune responses by producing extracellular adenosine. In this study, we employed gene-targeted mice to investigate the role of host-derived on antitumor immunity and tumor cell metastasis. We found ablation significantly suppressed growth ovalbumin-expressing MC38 colon cancer, EG7 lymphoma, AT-3 mammary tumors, B16F10 melanoma. The protective effect deficiency primary tumors was dependent CD8(+) T cells associated with an increased frequency...
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology neoplastic cells. It is now clear that can succumb some anticancer therapies by undergoing peculiar form cell death characterized an increased...
Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast (TNBC). Integrating spatial resolution of cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification TNBC, implications current therapies including checkpoint blockade. TNBCs an immunoreactive exhibited tumoral infiltration granzyme B+CD8+ T (GzmB+CD8+ cells), a type 1 IFN signature, and elevated multiple...
CD73 inhibits antitumor immunity through the activation of adenosine receptors expressed on multiple immune subsets. also enhances tumor metastasis, although nature subsets and receptor subtypes involved in this process are largely unknown. In study, we revealed that A2A/A2B antagonists were effective reducing metastasis tumors expressing endogenously (4T1.2 breast tumors) when was ectopically (B16F10 melanoma). A2A(-/-) mice strongly protected against indicating host A2A enhanced...
Immunotherapy is rapidly emerging as a cancer treatment with high potential. Recent clinical trials anti-CTLA-4 and anti-PD-1/PD-L1 antibodies (mAbs) suggest that targeting multiple immunosuppressive pathways may significantly improve patient survival. The generation of adenosine by CD73 also suppresses antitumor immune responses through the activation A2A receptors on T cells natural killer (NK) cells. We sought to determine whether blockade could enhance efficacy anti-PD-1 mAb. expression...
Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR has largely unsuccessful to date, partly because tumor-induced immunosuppressive mechanisms, adenosine production. Previous studies shown that generated by tumor potently inhibits endogenous antitumor cell responses through activation 2A receptors (A2ARs). Herein, we observed resulted...
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,...
Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe profile of A2A receptor inhibitors (A2ARi) Parkinson disease. Metastasis main cause cancer-related deaths worldwide, and therefore we have studied experimental spontaneous mouse models melanoma breast metastasis demonstrate efficacy mechanism a combination A2ARi with anti-PD-1 monoclonal antibody (mAb). This significantly reduces...
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed some patients, and critical features infiltrate remains unresolved. This study examined TIL density, composition organization together PD-1 PD-L1 expression freshly collected paraffin-embedded tissues from 125 patients invasive primary BC. Tumor...