RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cells

2018 ◽  
Author(s):  
Gianni Monaco ◽  
Bernett Lee ◽  
Weili Xu ◽  
Seri Mustafah ◽  
You Yi Hwang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Mrna Abundance ◽  
Rna Seq ◽  
Human Immune

scholarly journals RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types

Cell Reports ◽  
2019 ◽  
Vol 26 (6) ◽  
pp. 1627-1640.e7 ◽  
Author(s):  
Gianni Monaco ◽  
Bernett Lee ◽  
Weili Xu ◽  
Seri Mustafah ◽  
You Yi Hwang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Mrna Abundance ◽  
Rna Seq ◽  
Human Immune

Activation of human immune cells by the oncolytic parvovirus H-1 combined with chemotherapeutic or targeted agents

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
M Moehler ◽  
M Sieben ◽  
S Roth ◽  
B Leuchs ◽  
C Dinsart ◽  
...  
Keyword(s):  
Immune Cells ◽  
Targeted Agents ◽  
Human Immune

scholarly journals 601 Development of improved small molecule STING agonists suitable for systemic administration

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A636-A636
Author(s):  
Maciej Rogacki ◽  
Stefan Chmielewski ◽  
Magdalena Zawadzka ◽  
Jolanta Mazurek ◽  
Katarzyna Wnuk-Lipińska ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Small Molecule ◽  
Immune Cells ◽  
Systemic Administration ◽  
Cytokine Release ◽  
Major Player ◽  
Human Immune ◽  
New Generation ◽  
Dose Dependent ◽  
Complete Tumor

BackgroundStimulator of Interferon Genes (STING) is a major player in the activation of robust innate immune response leading to initiation and enhancement of tumor-specific adaptive immunity. Several clinical and pre-clinical programs have shown that activation of the STING pathway triggers immune-mediated antitumor response. Although vast majority of programs focus on development of analogues of the endogenous STING ligands, their chemical nature and stability often limit their use to local administration. Herein, we present recent results from the development of our selective non-nucleotide, non-macrocyclic, small molecule direct STING agonists, suitable for systemic administration, characterized by improved activity in human immune cells.MethodsBinding to recombinant STING protein was examined using FTS, MST, FP and crystallography studies. Phenotypic screen was performed in THP-1 Dual reporter cells. Mouse bone marrow-derived dendritic cells (BMDC) were obtained from C57BL/6 mice and differentiated with mIL-4 and mGM-CSF. STING agonists were administered into BALB/c mice and cytokine release was measured in plasma. Additionally, mice were inoculated with CT26 murine colon carcinoma or EMT6 murine breast carcinoma cells and the compound was administered, followed by the regular tumor growth and body weight monitoring.ResultsRyvu’s small-molecule agonists demonstrate strong binding affinity to recombinant STING proteins across all tested species. The compounds bind to all human STING protein variants and trigger pro-inflammatory cytokine release from human immune cells regardless of the STING haplotype. Moreover, new generation of developed agonists show significantly improved binding to human protein as well as in vitro activity on human cells. Systemic, intravenous in vivo administration leads to a dose-dependent upregulation of STING-dependent pro-inflammatory cytokines, which results in a dose-dependent antitumor efficacy observed in CT26 and EMT6 mouse cancer models, leading to complete tumor remissions in all treated animals. Furthermore, observed efficacy is accompanied by development of a lasting immunological response demonstrated by lack of tumor engraftment or a delayed tumor growth in cured animals challenged with repeated inoculation of cancer cells.ConclusionsNew generation Ryvu’s STING agonists are strong and selective activators of STING-dependent signaling in both mouse and human immune cells promoting anti-tumor immunity. Treatment with Ryvu’s small-molecule STING agonists leads to engagement of the immune system which results in a complete tumor remission and development of immunological memory of the cancer antigens. The compounds show good selectivity and ADME properties enabling development for systemic administration. In addition developed compounds maintain small functional handles amenable to linker attachment making the series suitable for versatile development as single agents, for combinations with immunotherapies or as targeted agents.

AB0057 Influence of PVA coated nanoparticles on survival and functionality of human immune cells

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 640.17-640
Author(s):  
C. Strehl ◽  
T. Gaber ◽  
M. Wagegg ◽  
M. Jakstadt ◽  
M. Hahne ◽  
...  
Keyword(s):  
Immune Cells ◽  
Coated Nanoparticles ◽  
Human Immune

Abstract MP44: A Novel And 2 Known Differentially Expressed MicroRNAs Were Identified In Peripheral Blood Mononuclear Cells Of Patients With Hypertension Associated With Metabolic Syndrome

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Olga Berillo ◽  
Kugeng Huo ◽  
Julio C Fraulob-Aquino ◽  
Chantal Richer ◽  
Na Li ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background: Hypertension (HTN) is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune cells. Whether miRNAs play a role in the activation of immune cells in hypertension complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) miRNAs and their mRNA targets in PBMCs of patients with hypertension complicated or not with metabolic syndrome (MetS) or chronic kidney disease (CKD). Methods: Normotensive subjects and patients with hypertension (HTN) associated or not with at least 2 other features of MetS or CKD were studied (n=15-16). PBMCs were isolated from blood, RNA extracted for small and total RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. MiRDeep2 was used for novel miRNAs prediction, miRNA annotation and counting. TargetScan 7.07 was used to predict DE miRNA targets with weighted context score percentile >50%. DE genes miRNAs and mRNAs were identified with fold change (FC) >1.5 and P <0.005. DE miRNAs with FC>2 and mean read count number (MRCM) >500, and with predicted targets with MRCM>300 were validated by reverse transcription-quantitative PCR (RT-qPCR). Results: DE miRNAs, mRNAs and non-coding RNAs were identified in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 miRNAs target 3 mRNAs in NTN, 57 miRNAs target 55 mRNAs in MetS and 3 miRNAs target 2 mRNAs in CKD. DE miR-409-5p (FC: 0.54±0.10 vs 1.00±0.09, P <0.05), miR-411-5p (FC: 0.40±0.06, vs 1.00±0.11, P <0.001) and the novel miR-pl-86 (FC: 1.96±0.17 vs 1.00±0.15, P <0.05) in MetS vs NTN were validated by RT-qPCR. RNA-seq data were correlated with RT-qPCR for miR-409-5p (R 2 =0.40, P <2.4E-07, n=55), miR-411-5p (R 2 =0.55, P <1.1E-10, n=55), miR-pl-86 (R 2 =0.37, P <5.5E-07, n=56). Conclusion: This study showed that DE miR-409-5p, miR-411-5p and miR-pl-86 may play a role in HTN associated with MetS.

Multi tissue processing for single cell sequencing of human immune cells v1

2021 ◽  
Author(s):  
Daniel Rainbow ◽  
Sarah Howlett ◽  
Lorna Jarvis ◽  
Joanne Jones
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Human Tissues ◽  
Single Cell Sequencing ◽  
Tissue Processing ◽  
Simultaneous Processing ◽  
Single Cell Rna Sequencing ◽  
Human Immune

This protocol has been developed for the simultaneous processing of multiple human tissues to extract immune cells for single cell RNA sequencing using the 10X platform, and ideal for atlasing projects. Included in this protocol are the steps needed to go from tissue to loading the 10X Chromium for single cell RNA sequencing and includes the hashtag and CiteSeq labelling of cells as well as the details needed to stimulate cells with PMA+I.

Single-cell RNA-seq profiling of individual Biomphalaria glabrata immune cells with a focus on immunologically relevant transcripts

2021 ◽  
Author(s):  
Hongyu Li ◽  
Abdullah A. Gharamah ◽  
Jacob R. Hambrook ◽  
Xinzhong Wu ◽  
Patrick C. Hanington
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Biomphalaria Glabrata ◽  
Rna Seq
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