Memory Improvement in clinical groups using Life-Logging Technologies

International audienc

Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vγ9Vδ2 Cells

Human V gamma 9V delta 2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of V gamma 9V delta 2 lymphocytes in chronic viral infections. Although V gamma 9V delta 2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate V gamma 9V delta 2 T cells to produce IFN-gamma but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-g, indicating that V gamma 9V delta 2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated V gamma 9V delta 2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with gamma delta cells in submicromolar concentrations of ZOL, we show that V gamma 9V delta 2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. V gamma 9V delta 2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-gamma and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by V gamma 9V delta 2 T cells have an antiviral potential in HCMVinfection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context

Higher Expression of CD44 in De Novo Diffuse Large B-cell Lymphoma Than in Richter Syndrome: USCAP 2022 Abstracts: Hematopathology (851-976)

Background: A subset of patients with chronic lymphocytic leukemia will experience transformation into Richter syndrome (RS), usually a diffuse large B–cell lymphoma (DLBCL). Clonal relationship based on IGHV analysis can determine a true RStransformation. Separating de novo DLBCL and RS is essential because novo DLBCL have a significantly better prognosis. The aim of this study is to find differentially expressed proteins in RS and de novo DLBCL.Design: The study comprised a total of 44 samples, specifically 18 RS and 26 de novo DLBCL of the non-GCB type. Among the RS, 8 were clonally related, 2 were clonally unrelated and for 8 no information was available regarding the clonal relationship. Initial proteomic screening analysis was processed through liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Among this 44 samples, 20 (10 RS and 10 de novo DLBCL) were analyzed by immunohistochemistry in order to evaluate the expression of CD44 and PKC-β. H-score was calculated with the semi quantitative evaluation of percentage of positive PKC-β cells multiplied by the weighted intensity of stain. All statistical analyses were performed using Student’s t-test. A p < 0.05 was considered statistically significant.Results: LC-MS/MS proteomic study identified a panel of proteins differentially expressed between RS and de novo DLBCLs (FDR<0.05), including CD44 (which was comparatively underexpressed in RS) and PKC-β (which was comparatively overexpressed in RS). The immunohistochemical study confirmed that CD44 expression is significantly higher in de novo DLBCL than in RS (p<0.002). PKC-β is also overexpressed in RS, but the difference is not significant.Conclusions: RS has a very poor prognosis and should not be confused with de novo DLBCL. This study demonstrated the interest of CD44 to immunophenotically distinguish RS from de novo DLBCL

Filling the Gap: The Immune Therapeutic Armamentarium for Relapsed/Refractory Hodgkin Lymphoma

Despite years of clinical progress which made Hodgkin lymphoma (HL) one of the most curable malignancies with conventional chemotherapy, refractoriness and recurrence may still affect up to 20&ndash;30% of patients. The revolution brought by the advent of immunotherapy in all kinds of neoplastic disorders is more than evident in this disease because anti-CD30 antibodies and checkpoint inhibitors have been able to rescue patients previously remaining without therapeutic options. Autologous hematopoietic cell transplantation still represents a significant step in the treatment algorithm for chemosensitive HL; however, the possibility to induce complete responses after allogeneic transplant procedures in patients receiving reduced-intensity conditioning regimens informs on its sensitivity to immunological control. Furthermore, the investigational application of adoptive T cell transfer therapies paves the way for future indications in this setting. Here, we seek to provide a fresh and up-to-date overview of the new immunotherapeutic agents dominating the scene of relapsed/refractory HL. In this optic, we will also review all the potential molecular mechanisms of tumor resistance, theoretically responsible for treatment failures, and we will discuss the place of allogeneic stem cell transplantation in the era of novel therapies

A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women

International audienceElevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL

Effect of millennial agro-pastoralism activities on pedogenetic processes in two altitudinal contexts of the western Alps

International audienc

Postprandial Triglyceride‐Rich Lipoproteins from Type 2 Diabetic Women Stimulate Platelet Activation Regardless of the Fat Source in the Meal

International audienceScope: The aim of this study is to examine whether postprandial (PP) triglyceride-rich lipoproteins (TGRL) secreted after a moderate fat intake would activate platelets differently according to their fatty acid (FA) composition. Methods and results: In a parallel single-blind randomized trial, 30 women with type 2 diabetes are assigned a breakfast containing 20 g lipids from butter versus hazelnut-cocoa spread (HCS) rich in palm oil. Blood samples are collected at fasting and 4 h PP. FA composition of fasting and PP TGRL and their effects on the activation of platelets from healthy blood donors are assessed. Both breakfasts similarly increase plasma ApoB-48, plasma, and TGRL triglycerides (p < 0.05). TGRL mean diameter increases after both breakfasts and is greater after the butter breakfast. Both breakfasts are rich in palmitic acid, and the HCS breakfast contains 45% oleic acid. TGRL FA composition reflects the dietary FA composition. Pre-incubation of platelets with fasting and PP TGRL increases collagen-stimulated aggregation (p < 0.01 vs control). Fasting and PP TGRL similarly increase agonist-induced thromboxane B 2 concentrations, and this effect is concentration-dependent for PP TGRL. Conclusion: PP TGRL from type 2 diabetic women after a palm-oil spread versus butter-based mixed meal induce similar acute in vitro platelet activation

Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: a study of the French Innovative Leukemia Organization

International audienc