Project description:This study investigates the role of dendritic cells (DCs) in anti-tumor immunity, focusing on the phosphatase SHP-1 and its regulation of signaling pathways and interactions with CD8+ T cells. Using conditional knockout mouse models and single-cell transcriptomics, we show that SHP-1 loss in conventional type 1 dendritic cells (cDC1s) and macrophages disrupts interferon responses, antigen presentation, and migratory programs, leading to impaired tumor rejection and reduced efficacy of PD-1 blockade. These findings provide mechanistic insights into dendritic cell biology within the tumor microenvironment (TME) and identify SHP-1 as a key regulator with implications for the design of DC-based cancer immunotherapies.
Project description:SPP1 stimulation of human leukocytes drives proinflammatory monocyte activation and differentiation of dysregulated CD274(PDL-1)pos neutrophil phenotype.
Project description:4 groups of mice : Control, antibiotics, antibiotics + 4days of recolonization, antibiotics + 4days of recolonization + Enterocloster clostridioformis. Tumor draining lymph node were harvested after CFSE injection were harvested and CFSE+ cells were sorted and proccessed in order to generate single cell RNA-sequencing using BD Rhapsody mouse immune response targeted panel. Groups were barcoded using BD Rhapsody Multiplexing Kit.
Project description:scRNAseq of HPMCs isolated ex vivo from 3 Patients. Targeted scRNASeq was applied using BD onco Panel with a additional genes. Purpose of the experiment was to characterize HPMC phenotype ex vivo and compare with the phenotype observed in RNAseq of HPMCs treated with IL17A and TNF.
Project description:Mice were infected with the pancreatic cancer cell line Pan02 (into their pancreas). 30 days later, pancreas was extracted, cells digested and BD Rhapsody RNAseq targeted against the MM immune panel was performed.
Project description:As pancreatic ductal adenocarcinoma (PDAC) is the deadliest solid cancer, and new immunological therapies have only marginally improved patient survival, we aimed at better understainding the immunological fingerprint of this disease. PDAC development involves inflammatory reprogramming and bacterial colonization, conditions that influence the adaptation of mucosa-associated invariant T cells (MAIT). We investigated MAIT signatures in patients with PDAC, chronic pancreatitis (CP), a risk factor for PDAC, and healthy donors (HD) using high-dimensional single-cell techniques, complemented by serum proteomics and multicolor histology. In our manuscript, we identify for the first-time human effector MAIT1 cells likely involved in protecting against PDAC. We characterize the transcriptional, phenotypic, and metabolic signatures of human MAIT1 compared to MAIT17-like cells, their adaptation to the PDAC inflammatory microenvironment, and provide insights into mechanisms underlying MAIT1-mediated protection against PDAC.
Project description:We conducted single-cell gene expression analysis of neutrophils from mouse tumors with and without microbial treatment to investigate neutrophil response in the tumor microenvironment (TME). Briefly, tumor-infiltrating Ly6G+CD11b+ neutrophils were isolated from unmanipulated tumors (resting), tumors treated with a vehicle control (control), and tumors treated with S. aureus bioparticles (stimulated) 24 hours after treatment. To survey the whole spectrum of the TME, we also isolated and sequenced non-neutrophil leukocytes in each sample.
Project description:This study investigates the mechanism underlying increased morbidity in individuals with chronic inflammatory conditions upon a secondary inflammatory challenge. Using mouse models, we identified a pronounced expansion of circulating immature neutrophils during chronic inflammation via single-cell RNA sequencing. Functional assays revealed these neutrophils are dysregulated. We established their causal role in exacerbating immunopathology and demonstrated that therapeutic intervention with antibodies or small molecules to block their migration or function significantly reduces tissue damage. This work defines a pathological cell population and proposes a novel therapeutic strategy for patients with chronic inflammatory diseases.
Project description:Processed single-cell datasets from Pdcd1-CreERT2 × Rosa26-tdTomato fate-mapping mice bearing subcutaneous LLC allografts and treated with CTX, anti-PD-1, or both. We provide count matrices, cell-level annotations, and per-cell TCR clonotypes; raw reads for transcriptome, sample-tag, and TCR libraries are deposited under ENA BioProject PRJEB100721. This resource profiles PD-1 lineage cells, highlighting therapy-dependent changes in progenitor-exhausted CD8 T cells and TCR clonotype dynamics.
Project description:The data here represent two Single-Cell experiments performed to understand the roles of PROS1 in bronchial epithelial cells and monocytes, infected by SARS-CoV-2. The CVR EXP5 contains epithelial cultures grown on Air-Liquid Interface as mock or infected by the delta variant of SARS-CoV-2 (Delta B.1.617.2), and cocultures of mock or infected epithelium with CD14 monocytes. Some of these cultures were also supplemented with PROS1, to study the effects of the protein during infection. The CVR EXP1 contains cultures of PBMCs cultured in presence of SARS-CoV-2 variant (BetaCoV/England/02/2020/EPI_ISL_407073 ), with or without PROS1 supplementation. CVR EXP5 libraries were prepared using the Whole transcriptome Analysis and Sample Tag library Preparation kit (BD 633801), as per manufacture’s protocol (2019 version). CVR EXP1 libraries of 399 genes were prepared using BD Rhapsody Targeted mRNA and the Tag Amplification Kit (no. 633774) and primers from the BD Rhapsody Immune response Panel Hs (399 genes, BD 633750), as per manufacture’s protocol.