Project description:In this study we wanted to identify baseline predictors of successful vedolizumab therapy in patients with inflammatory bowel disease.
Project description:Studying differences in responders and non-responders to therapy in inflammatory bowel disease (IBD) patients (crohn's disease and ulcerative colitis)
Project description:Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We experimentally tuned flow profiles in vitro (microfluidics) and in vivo (zebrafish) and demonstrated that efficient uptake of tEVs occurs in endothelial cells subjected to capillary-like hemodynamics. Such flow profiles partially reroute internalized tEVs towards non-acidic and non-degradative Rab14-positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro-angiogenic transcription factors in flow-stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that capillary-like flow profiles potentiate the pro-tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre-metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics. This set of experiments represents RNAseq of HUVEC cells subjected to 400 µm/s flow versus no flow (static conditon).
Project description:Metastases arise from a multi-step process during which tumor cells change their mechanics in response to microenvironmental cues. While such mechanical adaptability could influence metastatic success, how tumor cell mechanics directly impacts intravascular behavior of circulating tumor cells (CTCs) remains poorly understood. In the present study, we demonstrate how the deformability of CTCs affects hematogenous dissemination and identify the mechanical profiles that favor metastatic extravasation. Combining intravital microscopy with CTC-mimicking elastic beads and mechanically-tuned tumor cells, we demonstrate that the inherent properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as the key property that governs CTC circulation and arrest patterns. We further demonstrate that cellular viscosity is required for efficient extravasation and find that properties that favor extravasation and subsequent metastatic outgrowth can be opposite. Altogether, we identify CTC viscosity as a key biomechanical parameter that shapes several steps of metastasis.
Project description:P. tricornutum (Bacillariophyta, Pennatae, NEPCC640) was obtained from the Algal Center of the Institute of Oceanology of the Chinese Academy of Sciences. The cells were cultured in a modified f/2 medium (Guillard, 1975) at 20 +/- 1C, and illuminated with 120 umol photon m-2 s-1 under a 12:12 light: dark cycle. Flasks were shaken by the researchers twice a day at the fixed times. Experiments were conducted in triplicate in 3L sterilized and acid-washed Erlenmeyer flask containing 2L medium. The equipment used in this study is similar to the ones used in previous ocean acidification research (Fu et al., 2007; Hutchins et al., 2007; Wu et al., 2010). Prior to inoculation, the mediums were treated by different CO2 concentrations. The low CO2 medium was bubbled with ambient air of about 400 ppmv (low CO2, LC) and the high CO2 medium was bubbled with pre-mixed air-CO2 mixtures (1000 ppmv; high CO2, HC) from a plant growth CO2 chamber (HP400G-D, Ruihua Instrument & Equipment Ltd, Wuhan, China) with a variation of less than 5%. Semi-continuous cultures were used to maintain the pH stability during P. tricornutum growth in the present study, All the cultures were diluted to 1x104 cells mL-1 with fresh medium and pre-acclimated to the desired CO2 level every 24 h to maintain an exponential growth phase and minimize pH fluctuations of the cells. Cultures were harvested after 8 months of semi-continuous incubation. Significant differences between the carbonate systems in different cultures.
Project description:Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, we characterize the molecular and functional response of human NK cells and pan T cells to two NPs that are commonly used in biomedical applications: ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs. Bulk RNA-sequencing analysis showcase that PLGA NPs trigger a transcriptional priming towards activation in NK and T cells. While PLGA NPs improved NK cells anti-tumoral functions in a cytokine-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation . Altogether, we identified PLGAs NPs as suitable and promising candidates for further targeting approaches aiming to reactivate the immune system of cancer patients.
Project description:This study reports two unrelated patients with a combined immunodeficiency. Whole-exome sequencing of both patients, their healthy parents and siblings identified a single de novo missense variant in ITPR3 (NM_002224.3:c.7570C>T, p.Arg2524Cys) in both index cases. While the mRNA level in patients remained the same as in healthy siblings and controls, the level of protein expression was diminished. It was also shown that the ITPR3 heterozygous p.Arg2524Cys mutation impairs calcium flux function in dermal fibroblast of one patient and in a knock-in Jurkat T cell line. Two additional patients with related phenotypes and the same mutation were further identified and described in the study. The present dataset corresponds to the RNAseq performed on PBMC of patient 2 of the study and healthy controls.
Project description:The study describes two independent cases of NCKAP1L-deficiency, both carrying homozygous non-sense or splice variants in the NCKAP1L gene. The patients presented a phenotype of immunodeficiency, lymphoproliferation and hyperinflammation with features of Hemophagocytic Lymphohistiocytosis (HLH).
Project description:RNAseq on PBMC of three patients with Familial Hemophagocytic Lymphohistiocytosis Type 5 (FHL5) and three age and sex-matched controls.
Project description:This study aimed to identify a biomarker predicting response to ustekinumab therapy. Therefore, we used transcriptomic data (colonic and ileal tissue, CD4 T-cell and CD14 monocytes), which we integrated through Multi-Omics Factor Analysis.