Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Allergic mediator histamine confers immunotherapy resistance in cancer patients via histamine receptor 1 on macrophage

ABSTRACT: How to revive anti-tumor immunity in cancer patients is an unmet challenge. Retrospective screening of common medications revealed that patients who took antihistamines during immunotherapy treatment had significantly improved survival. We further uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in tumor microenvironment to cause T-cell dysfunction. HRH1 activation in macrophages inhibits proinflammatory signaling and dysregulates fatty acid metabolism. HRH1 also increases membrane expression of immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) in macrophages, which renders CD8+ T-cells dysfunctional. Knockout HRH1 or antihistamine treatment negated the immunosuppressive activity of the macrophages, revitalized T-cell cytotoxic function, and restored immunotherapy response. Both animal and human data showed that allergy facilitated tumor growth and induced immunotherapy resistance via histamine/HRH1 axis, underscoring the tumor-p rone activity of allergy. These findings demonstrate that pre-existing allergy in cancer patients can dampen response to immunotherapies and warrant perspective investigation of antihistamines as an adjuvant agent for combinatorial immunotherapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE161484 | GEO | 2020/11/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effect of depletion of histamine receptor HRH1 on gene expression of histamine treated human endothelial cells

Project description:To investigate the function of histamine signal perceived by HRH1 in the regulation of endothelial angiogenic process, we knocked down HRH1 using shRNA from histamine treated endothelial cells.

2022-08-28 | GSE211726 | GEO

Blockade of histamine receptor H1 augments immune checkpoint therapy by enhancing MHC-I expression in pancreatic cancer cells

Project description:Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective in managing certain cancers, its efficacy in pancreatic ductal adenocarcinoma (PDAC) remains limited. Previous studies have indicated that histamine and histamine receptor H1 (HRH1) can suppress immunity by affecting immune cells. This study uncovered an unexplored role of HRH1 intrinsic to tumor cells in PDAC. When HRH1 specific to tumor cells was inhibited in PDAC mouse models, there was a noticeable increase in MHC-I expression in these cells via the activation of cholesterol biosynthesis signaling. This augmented the infiltration and efficacy of cytotoxic CD8+ T cells, synergizing anticancer immunity and mitigating resistance to ICB treatment. Our results highlight that HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

2023-12-26 | GSE251639 | GEO

Allergic mediator histamine confers immunotherapy resistance in cancer patients via histamine receptor 1 on macrophage

Project description:Allergic mediator histamine confers immunotherapy resistance in cancer patients via histamine receptor 1 on macrophage

| PRJNA678382 | ENA

Effect of histamine on human keratinocytes

Project description:Genome-wide analysis of gene expression after stimulation with histamine to assess the main processes, molecular functions and cellular components affected as well as genes related to skin barrier function. HaCaT cells were exposed to histamine (1ug/ml) for 24h. The cells were lysed, total RNA was extracted and microarray study was performed on Illumina HT12 platform.

2013-12-01 | E-GEOD-41585 | biostudies-arrayexpress

Evaluation of the impact of neoplastic histamine secretion on melanoma progression

Project description:We previously showed that transgenic enhancement of histamine production in B16-F10 melanomas strongly supports tumor growth in C57Bl/6 mice (Cancer Res, 2005 Pos et al.). In this array experiment, gene expression profiles of transgenic mouse melanomas, secreting different amounts of histamine, were compared by whole genome microarrays. Keywords: genetic modification

2007-09-15 | GSE8541 | GEO

Placental Gene Expression in Response to Histamine and Oxygen

Project description:Maternal Blood histamine levels are tightly controlled in normal pregnancy. However, in specific complications of human pregnancy such as pre-eclampsia the levels of both placental and maternal blood histamine increase. Increasing blood histamine levels nonetheless, have been associated with oxidative stress, endothelial dysfunction, abnormal tissue growth, and Th1/TH2 imbalance, which are also linked to pre-eclampsia. Little is known of the molecular responses in the placenta to the prolonged exposure to increasing histamine levels in the presence of changing oxygen concentrations. We used microarray to detail the global programme of placental gene expression in response to histamine and oxygen and identified distinct classes of regulated genes underlying the molecular functions of histamine in the placenta.

2017-06-01 | GSE74446 | GEO

Translation State Array Analysis of Histamine Stimulated Human Endothelial Cells

Project description:Confluent human umbilical vein endothelial cells (HUVECs) were exposed to histamine (100 mM) for 2 hours. Ribosomal profiling via gradient centrifugation and fractionation was used to separate monosome, or under-translated, and polysome, or actively translated, mRNA species that were then used to probe cDNA arrays, a process known as Translation State Array Analysis (TSAA). Four samples were obtained from these experiments, control monosome, control polysome, histamine monosome and histamine polysome. Using the normalized signal intensities from the GeneFilters, we calculated a translation index, or measure of movement of an mRNA molecule from the monosome to the polysome fraction upon stimulation. This calculation was made as follows: (histamine polysome/histamine monosome)/(control polysome/control monosome). Translational indices greater than 2.5 (upregulated) or lower than 0.4 (downregulated) were chosen for further study. Keywords: Translation State Array Analysis

2006-07-27 | GSE5385 | GEO

RNA of murine macrophages and neutrophils treated with LPS and VISTA

Project description:V-domain immunoglobulin suppressor of T-cell activation (VISTA) has emerged as a unique immunoregulatory receptor on cells of the myeloid lineage. Agonizing VISTA on myeloid cells has recently been demonstrated to have a profound effect on dampening inflammatory responses. VISTA has been proposed to function both as a ligand and as a receptor, yet the role of VISTA as a ligand has been largely ignored. In this experiment, macrophages and neutrophils were isolated from mice and treated with LPS and VISTA to examine the effect of VISTA in dampening acute inflammation.

2022-12-02 | E-MTAB-10856 | biostudies-arrayexpress

Smoking-induced Reprogramming of Histamine Metabolism Genes in the Human Small Airway Epithelium

Project description:Smoking is associated with increased airway histamine responsiveness and elevated histamine levels. Transcript levels of histidine decarboxylase (HDC; histamine synthesis) and histamine N-methyltransferase (HNMT; histamine degradation) were evaluated in small airway epithelial (SAE) cells obtained from smokers or non-smokers. Histamine+ SAE cells increased in smokers compared to nonsmokers (p< 0.03). HDC transcript levels were elevated in smokers compared with non-smokers when comparing both bulk RNA from SAE (p< 0.03) and single cell HDC transcripts in mast cells (p<10-6). Elevated HDC transcript levels in mast cells corre-lated with elevated IL33 transcript levels in smoker SAE basal cells, and elevated transcript levels of the IL33 receptor, IL1RL1, in mast cells. In contrast to HDC, transcript levels of HNMT were decreased (p<10-4) in smoker SAE. Significant decreases in HNMT transcript levels were found broadly across SAE differentiated cell types. An in vitro SAE culture model treated with cigarette smoke extract reduced HNMT transcript levels (p<0.05). Together, the data suggests that smoking results in an accumulation of mast cells, elevated expression of histamine-synthesizing mast cell HDC, and a decrease in histamine-degrading HNMT transcript levels broadly in the epithelium. These smoking induced changes are likely contributors to elevated histamine levels in the airways of smokers.

2020-08-03 | GSE154136 | GEO

RNA-seq of Histamine stimulated HUVECs infected with shNT or shH1R

Project description:To investigate the mechanism of histamine H1 receptor (H1R)- mediated proliferation and angiogenesis of endothelial cells, mRNA profiles of HUVEC cells transduced with shNT or shH1R under histamine treatment for 9 hrs were generated by deep sequencing, in replicate, using Illumina GAIIx. We identified the upregulation of genes in several pathways including angiogenesis, proliferation and migration that could be responsible for the increased tube formation in histamine treated shNT expressing HUVEC cells

2020-03-22 | GSE147333 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data