Paulo Cordeiro

CHU Ste-Justine Research Centre · Cancer

Background Allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard of care for chemotherapy-refractory leukemia patients, but cure rates are still dismal. To prevent leukemia relapse following HSCT, we aim to improve the early graft-versus-leukemia effect mediated by natural killer (NK) cells. Our approach is based on the ado...

Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a pro...

Targeted immunotherapy has improved the outcome of patients with high-risk neuroblastoma (NB). However, immune escape of tumor cells still occurs and about 40% of NB patients relapse and die from their disease. We previously showed that natural killer (NK) cell stimulation by Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC) inc...

Despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT), the outcome of children with relapsed acute lymphoblastic leukemia (ALL) has not significantly improved over the last 2 decades. About 50% of children with relapsed leukemia still die from their disease and ALL is still the first cause of death by cancer in childre...

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers...

High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the recent advent of disialoganglioside (GD2)-antibody treatment combined with interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF). Indeed, more than one third of the patients still die from this disease. Here, we developed a novel approach to impr...

Flow cytometry analysis of NK cell phenotype following overnight stimulation. Representative dot plot analysis of immunostaining with anti-CD56, anti-CD69, anti-TRAIL antibodies (gated on CD3- cells). (EPS)

NK cell phenotype was analyzed by flow cytometry following overnight stimulation with IL-15, IFN-α or activated pDCs. Box plots represent the distribution of the median fluorescence intensity (MFI) of the indicated markers (NKp30, NKp46, NKp44, Fas-L, Perforin and Granzyme B). Statistical analyses were performed using one-way analysis of variance....

Acute lymphoblastic leukemia (ALL) still frequently recurs after hematopoietic stem cell transplantation (HSCT), underscoring the need to improve the graft-versus-leukemia (GvL) effect. Natural killer (NK) cells reconstitute in the first months following HSCT when leukemia burden is at its lowest, but ALL cells have been shown to be resistant to NK...

Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplant immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number...

Some clinical characteristics of cord blood transplantation (CBT) might be explained by specificities in the reconstitution of immune subsets differing by their maturation stage or their implication in GVHD, tolerance or immune responses against tumor or infectious agents. Here, we compare the immune reconstitution of several of these subsets after...

CMV and varicella zoster virus (VZV) are significant causes of morbidity and mortality following umbilical cord blood transplantation (UCBT). However, the kinetics of reconstitution and protective potential of antiviral cell-mediated immune responses following UCBT remain poorly characterized. In this study, the reconstitution of CMV- and VZV-speci...

Physiological modulation of the immune system is required for foetal tolerance during pregnancy. However, this immune regulation might lead to impaired self-defence against pathogens. Indeed, pregnant women are more susceptible to newly encountered viruses comparing to non-pregnant women, as exemplified by the prevalence of severe complications in...

Cytomegalovirus (CMV) and varicella-zoster virus (VZV) are significant causes of morbidity and mortality following umbilical cord blood transplant (UCBT). Yet the kinetics of reconstitution and protective potential of antiviral cell-mediated immune responses following UCBT remain poorly characterized. Here, the reconstitution of CMV and VZV-specifi...

Plasmacytoid dendritic cells (pDC) are specialized dendritic cells, also known as IFN-α producing cells. pDC are key inducers of immune responses upon viral infections; the environment although modulate their phenotype and functions. We have shown that cord blood (CB) pDC are unable to produce IFN-α after stimulation while they retain the capacity...

Lymphoid differentiation and activation critically depend on cytokine stimulation and the interleukin-7 (IL-7) signaling in particular. Although it has been demonstrated that IL-7 may play a role in natural killer (NK) cell maturation, the effect of IL-7 stimulation on mature human NK cells has not been studied. We, therefore, investigated the expr...

Thymoglobulin is an antithymocyte globulin preparation used in hematopoietic stem cell transplantation (HSCT) to prevent rejection and graft-versus-host disease. Because natural killer (NK)-cell alloreactivity improves HSCT outcome, but only in patients receiving thymoglobulin, we investigated the in vitro effects of thymoglobulin on purified NK ce...

Exposure of human monocytic cells to herpes simplex virus type 1 (HSV-1) results in immediate up-regulation of interleukin (IL)-15 gene expression. However, the receptor involved in this induction is not known. Here, we provide evidence that this induction depends on TLR2-mediated signaling pathway. Through the use of small interfering RNAs (siRNAs...

Introduction: The interaction between natural killer cells (NK) and plasmacytoid dendritic cells (pDC) has been suggested to play a role during the early phase of the immune response to viral infections and tumors. NK cells can lyse tumor and virus‐infected cells and their cytolytic activity has long been known to be enhanced by interferon‐alpha (I...

Background: Antithymocyte globulin (Thymoglobulin, rabbit IgG) is widely used in hematopoietic stem cell transplantation (HSCT) to prevent rejection and graft-versus-host disease (GVHD). A beneficial effect of natural killer (NK)-cell alloreactivity on HSCT outcome has been described, but only in patients receiving ATG. We therefore investigated th...

The increased susceptibility of human newborns to infections is usually ascribed to the immaturity of the neonatal immune system. The neonatal immune system has never met microbial antigens, and thus the repertoire of its adaptative arm (T and B cells) is entirely pre-immune, or "naïve". However this neonatal pre-immune repertoire is similar to the...

IL-15 plays a seminal role in innate immunity through enhancing the cytotoxic function as well as cytokine production by NK and T cells. We have previously shown that exposure of PBMC as well as monocytic cells to different viruses results in immediate up-regulation of IL-15 gene expression and subsequent NK cell activation as an innate immune resp...

Latent membrane protein 1 (LMP-1) is an Epstein-Barr virus-encoded oncoprotein expressed in approximately 50-70% of nasopharyngeal carcinoma (NPC). Previous studies have shown that NPC-derived LMP-1 variants carrying 30 bp deletion and specific mutations in the 3'C-terminal region confer high oncogenic potential and a weak immunogenicity. Although...

TH1/TH2 cytokines' imbalance is critical to HIV-1 progression and pathogenesis. Opportunistic infections-related cytokine perturbations in the setting of highly active antiretroviral therapy (HAART) are unclear. The objective of this cross-sectional study was to identify the relationship between TH1/TH2 cytokines and viremia in HAART patients with/...

β-D-N-acetylhexosaminidases A (Hex A, αβ) and B (Hex B, ββ) cleave N-acetylglucosamine and N-acetylgalactosamine termini of glycoconjugates. Hex B hydrolyzes neutral substrates whereas Hex A also hydrolyzes electronegative substrates, including GM2 ganglioside, which accumulates in the neurons of patients with Tay-Sachs disease (TSD). We hypothesiz...

The GM2 gangliosidoses are a group of recessive disorders characterized by accumulation of GM2 ganglioside in neuronal cells. The genes responsible for these disorders are HEXA (Tay-Sachs disease and variants), HEXB (Sandhoff disease and variants), and GM2A (AB variant of GM2 gangliosidosis). We report the establishment of three relational locus-sp...

The GM2 gangliosidoses are a group of recessive disorders, which lead to the accumulation of GM2 ganglioside in neuronal cells. The genes responsible for these disorders are HEXA (Tay-Sachs disease and variants), HEXB (Sandhoff disease and variants) and GM2A (AB variant of GM2 gangliosidosis). We have established three relational locus-specific dat...