Jean-Sébastien Delisle

Jean-Sébastien Delisle
Université de Montréal | UdeM

About

102
Publications
8,747
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1,091
Citations
Citations since 2016
72 Research Items
945 Citations
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200

Publications

Publications (102)
Article
Background Allogeneic hematopoietic cell transplant (HCT) has curative potential in myeloma but remains hampered by high rates of relapse and chronic GVHD. We hypothesized that bortezomib (BTZ) as maintenance therapy after allo HCT could not only decrease the incidence of relapse but also the incidence and severity of chronic GVHD. Objective The p...
Article
Background: With the advent of new cellular and targeted therapies, treatment options for relapsed and refractory (r/R) lymphomas have multiplied and the optimal approach offering the best outcomes remains a matter of passionate debate. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is still considered a treatment o...
Article
Full-text available
Antigen-specific T cells expansion ex vivo followed by adoptive transfer enables the targeting of a multitude of microbial and cancer antigens. However, clinical scale T-cell expansion from rare precursors requires repeated stimulations which may lead to T-cell dysfunction and limited therapeutic potential. We used a clinically-compliant protocol t...
Article
Full-text available
The purpose of this retrospective study was to study the correlation between donor age (DA) and non-relapse mortality (NRM) and relapse incidence (RI) among patients treated with allogeneic hematopoietic cell transplantation (aHCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in a single Canadian center. Data from 125 consecut...
Article
Acute myeloid leukemia (AML) is a cancer that originates from the bone marrow (BM). Under physiological conditions, the bone marrow supports the homeostasis of immune cells and hosts memory lymphoid cells. In this review, we summarize our present understanding of the role of the immune microenvironment on healthy bone marrow and on the development...
Article
Full-text available
Despite novel drugs and autologous HCT, MM remains incurable, with short survival in patients with poor biological characteristics. Allo HCT may be curative in some patients but is hampered by high rates of toxicity and relapse. We hypothesized that bortezomib (BTZ), with its anti-myeloma and immunologic properties, could improve PFS and cGVHD afte...
Article
Background Despite high cure rates with frontline therapy for Hodgkin lymphoma (HL), about 30% of patients will relapse or have primary refractory disease (R/r). Autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care for R/r disease and alloHSCT is a curative option for patients in second relapse. Novel agents are being...
Preprint
Full-text available
Background. The stimulation and expansion of antigen-specific T cells ex vivo enables the targeting of a multitude of cancer antigens. However, clinical scale T-cell expansion from rare precursors requires repeated stimulations ex vivo leading to T-cell terminal effector differentiation and exhaustion that adversely impact therapeutic potential. We...
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T-cell dysfunction arising upon repeated antigen exposure prevents effective immunity and immunotherapy. Using various clinically and physiologically relevant systems, we show that a prominent feature of PD-1-expressing exhausted T cells is the development of cellular senescence features both in vivo and ex vivo. This is associated with p16INK4a ex...
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Studies in murine models show that subthreshold T cell receptor (TCR) interactions with self‐peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self‐peptide, as read‐out by cell surface levels of CD5, were associated with distinct effector potent...
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Age-related macular degeneration (AMD) in its various forms is a leading cause of blindness in industrialized countries. Here, we provide evidence that ligands for neuropilin-1 (NRP1), such as Semaphorin 3A and VEGF-A, are elevated in the vitreous of patients with AMD at times of active choroidal neovascularization (CNV). We further demonstrate tha...
Article
Acute myeloid leukemia (AML) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Using an original proteogenomic approach, we analyzed the major histocompatibility complex class I (MHC class I)-associated immunopeptidome of 19 primary AML samples and identified 58 tumor-specific antigens (TSAs...
Article
Full-text available
Over the last decades, cellular immunotherapy has revealed its curative potential. However, inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death, undermine adoptive cell t...
Preprint
Full-text available
Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cel...
Article
Introduction Rapid T cell reconstitution following hematopoietic stem cell transplantation is essential for protection against infections and has been associated with lower incidence of chronic graft-vs-host disease (cGVHD), relapse and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD an...
Article
Full-text available
Background The development of immunotherapies holds great promise for the treatment of refractory infections and cancer. Current approaches, although effective in many settings, have limitations that prevent their widespread use. Hence, several aspects require improvements, including the re-wiring of T-cell fates and function. T-cell dysfunction is...
Article
Full-text available
Rapid T cell reconstitution following hematopoietic stem cell transplantation (HSCT) is essential for protection against infections and has been associated with lower incidence of chronic graft-versus-host disease (cGVHD), relapse, and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and...
Article
Background Long‐term survival in patients progressing after tandem autologous‐allogeneic stem cell transplant (SCT) has been reported, suggesting a persistent graft‐vs‐myeloma (GvM) effect even after post‐transplant progression. Methods In order to confirm this observation, we updated the results of our previously published cohort of 92 newly diag...
Article
Haplo‐identical donors have been increasingly used as an alternative source of stem cells in patients with severe aplastic anemia in need of an allogeneic transplantation but lack a matched donor. Single cord blood (CB) transplant also offers a curative option for this disease but few adult patients have been reported due to low number of progenito...
Article
Full-text available
Background A better survival in patients with multiple myeloma (MM) progressing after tandem autologous (auto)/allogeneic (allo) hematopoietic stem cell transplantation (HSCT) has been previously reported (Htut M. et al. BBMT 2018), suggesting a persistent graft-versus-multiple myeloma (GvMM) effect even after relapse. We sought to confirm this obs...
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Over the last decades, T-cell immunotherapy has revealed itself as a powerful, and often curative, strategy to treat blood cancers. In hematopoietic cell transplantation, most of the so-called graft-vs.-leukemia (GVL) effect hinges on the recognition of histocompatibility antigens that reflect immunologically relevant genetic variants between donor...
Article
Background Benefits of cord blood (CB) transplantation include low rates of relapse and chronic graft-versus-host disease (cGVHD). However, CB use is rapidly declining because of delayed neutrophil recovery, high rates of infections and severe acute GVHD leading to high transplant-related mortality (TRM) and prolonged hospitalization. Several of th...
Article
Background: Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to...
Article
Full-text available
High-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (AHSCT) improves survival in patients with chemosensitive non-Hodgkin lymphoma (NHL). Determination of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) has contributed to improve patient selection while allowing for prediction of nonrelapse...
Article
The adoptive transfer of ex vivo-expanded T cells is a promising approach to treat several malignancies. Several lines of evidence support that the infusion of T cells with early memory features, capable of expanding and persisting after transfer, are associated with better outcomes. We report herein that exposure to exogenous TGFβ during human T-c...
Article
Full-text available
Graft‐versus‐host disease (GVHD) is a major cause of transplant‐related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T‐cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant...
Article
Background: Autologous hematopoietic stem cell transplantation (AHSCT) in the older population is associated with an increased risk of morbidity and mortality. Determination of the hematopoietic cell transplant comorbidity index (HCT-CI) has contributed to improve patient selection while allowing prediction of their non-relapse mortality (NRM). Th...
Article
On-chip high-throughput phenotyping of single cells has gained a lot of interest recently due to the discrimination capability of label-free biomarkers such as whole-cell deformability and refractive index. Here we present on-chip Refractive Index Cytometry (RIC) for whole-cell deformability at a high measurement rate. We have further exploited a p...
Article
The analysis and validation of flow cytometry-based biomarkers in clinical studies are limited by the lack of standardized protocols that are reproducible across multiple centers and suitable for use with either unfractionated blood or cryopreserved PBMCs. Here we report the development of a platform that standardizes a set of flow cytometry panels...
Article
BACKGROUND Following solid organ or hematopoietic cell transplantation, refractory opportunistic viral reactivations are a significant cause of morbidity and mortality but can effectively be controlled by virus‐specific T‐cell transfer. Among effective and safe strategies is the use of “third‐party” (neither from the transplant donor nor recipient)...
Article
Introduction: Multiple myeloma (MM) remains incurable with standard therapies. Allogeneic stem cell transplantation (alloSCT) is the only curative treatment for these patients. We hypothesized that bortezomib (BTZ) consolidation after tandem autologous stem cell transplantation (ASCT) and nonmyeloablative (NMA) alloSCT could improve quality of resp...
Article
Cord blood (CB) transplants have fallen into disfavor in large part due to low cell dose leading to prolonged hospitalizations and high transplant related mortality (TRM). UM171, a novel and potent agonist of hematopoietic stem cell (HSC) self-renewal could solve this major limitation, allowing for CB's important qualities of lower risk of chronic...
Article
Full-text available
Chronic graft-versus-host disease (cGVHD) is a major complication affecting 50 to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation. Current cGVHD therapies are neither specific nor curative and patients are typically maintained for several months to years under immunosuppressive regimens that are associated with impo...
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Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-β on T cell proliferation, activation, and...
Article
This paper presents a novel microphotonic sensor based on silicon technologies for high-throughput single cell measurements. It employs a highly sensitive Fabry-Pérot resonant cavity to extract cellular refractive index information. The integrated large cross-section rib waveguides provide a single-mode like behavior important for resonant cell sen...
Article
Cord blood (CB) transplants are hampered by low cell dose and high transplant related mortality (TRM). UM171, a novel and potent agonist of hematopoietic stem cell (HSC) self-renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. Hence, we initiated a clinical trial to...
Article
Full-text available
Global investments in cellular immunotherapies reflect their curative potential. Our landscape of clinical trials will aid developers, investors, adopters and payers in planning for adoption and implementation along realistic time horizons. Trend data enable stakeholders to adapt their business models and capacity to bring immunotherapies to the cl...
Article
Full-text available
Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-relat...
Article
Full-text available
Posterior reversible encephalopathy syndrome (PRES) is a rare and generally reversible neurological disorder that was first described in the field of hematopoietic stem cell transplantation (HSCT) by Sloane et al.¹ To date, its pathogenesis remains unclear but seems to be related to dysregulation of cerebral blood flow with endothelial dysfunction,...
Article
Background: Polyomavirus-associated nephropathy (PVAN) following BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulati...
Article
Many new therapeutic agents have been approved for follicular lymphoma (FL) but none appear to be curative. Despite novel agents, some patients (pts) experience early relapse, become chemorefractory or suffer transformation into more aggressive lymphomas. Options for these pts are limited. High dose chemotherapy with autologous stem transplant (ASC...
Article
Introduction. Haploidentical donors may resolve the shortage of available HLA-matched donors for the treatment of patients with blood cancers in need of a hematopoietic stem cell transplantation (HSCT). However, to prevent graft-versus-host disease (GVHD), haploidentical HSCT requires alloreactive T-cell depletion or suppression. We developed an ex...
Article
Introduction: Allogeneicstem cell transplantation (alloSCT) is the only curative modality for newly diagnosed multiple myeloma (NDMM) patients (pts). However, we have previously shown in a large cohort of 92 pts that relapse remains common (49%) and the incidence/severity of chronic GVHD is significant (79%) after tandem auto-allo SCT in NDMM pts (...
Article
Introduction: Over the last decade transplant programs have seen a significant increase in the median age of autologous hematopoietic stem cell transplant (AHSCT) recipients (McCarthy et al. 2013).We recently demonstrated thathigh-dose chemotherapy (HDT) followed by AHSCT was safe and well tolerated in elderly patients withchemosensitivenon-Hodgkin...
Article
To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the...