Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IL-12 induces myeloid cells in situ to cross-present antigen

ABSTRACT: Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions.

ORGANISM(S): Mus musculus

PROVIDER: GSE29164 | GEO | 2012/04/23

SECONDARY ACCESSION(S): PRJNA140083

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

IL-12 induces myeloid cells in situ to cross-present antigen

Project description:Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions. Samples were collected at 3 days and 7 days from tumors treated in-vivo with no treatment, Mock pmel-1 CD8+ cell treatment, or IL-12 pmel-1 CD8+ cell treatment. There were 4 biological replicates of each sample type. There were a total of 24 samples.

2012-04-22 | E-GEOD-29164 | biostudies-arrayexpress

Effect of rapamycin on murine subcutaneous MC38 tumor cell populations

Project description:To determine differential metabolic gene expression in distinct cell populations from subcutaneous MC38 tumors at baseline and in response to rapamycin, tumors from mice treated with vehicle or rapamycin were harvested, reconstituted to single cell suspensions, and flow sorted into cancer cell (CD45-), tumor-associated macrophage (TAM, CD45+ CD11b+ Ly6G- Ly6C lo F4/80 hi), monocytic myeloid-derived suppressor cell (M-MDSC, CD45+ CD11b+ Ly6G- Ly6C hi), CD8 T cell (CD45+ CD3+ CD8a+), and CD4 T cell (CD45+ CD3+ CD8a-) populations. RNA was extracted and transcripts were quantified by the NanoString nCounter Metabolic Pathways Panel.

2021-02-26 | GSE165223 | GEO

Heterogeneity of Ly6G+Ly6C+ myeloid-derived suppressor cell (MDSC) infiltrates during S. aureus biofilm infection

Project description:The two immune cell populations Myeloid-derived suppressor cells (MDSCs), monocytes (MONO) and neutrophils (PMNs) are difficult to differentiate because of shared surface marker expression. Here we utilize the integrin receptor CD11b combined with conventional Ly6G and Ly6C expression to more accurately separate cellular populations via FACS. Then we apply high-throughput RNA Sequencing to Ly6G+Ly6C+CD11bhigh MDSC, Ly6G+Ly6C+CD11blow PMN and Ly6G-Ly6C+ monocyte populations. A total of 6,466 genes were significantly differentially expressed in MDSCs vs. monocytes, whereas only 297 genes were significantly different between MDSCs and PMNs. A number of genes implicated in cell cycle regulation were identified, and in vivo EdU labeling revealed that over 75% of MDSCs proliferated locally at the site of S. aureus biofilm infection.

2018-10-03 | GSE118796 | GEO

G-CSF mobilizes CD34+ regulatory monocytes that inhibit Graft-versus-Host Disease

Project description:Administration of G-CSF mobilizes a unique population of CD11b+Ly6C+CD34+mature monocytes that can inhibit GVHD in murine models of BMT via an iNOS-dependent mechanism. The transcriptional profiles of flow sorted lineage-CD11b+CD34+ cells from G-CSF treated mice were compared with conventional splenic Ly6C+ and Ly6C- monocytes, progenitor cells and cultured myeloid-derived suppressor cells. Further comparisons were made with lineage-CD11b+CD34+ cells from G-CSF treated mice that had been grown in culture or that were derived from iNOS ko mice. We used microarrays to detail the global programme of gene expression underlying diffrenetiation of each of these cell types Lin-CD11b+CD34+ populations were isolated directly from the spleens of G-CSF-treated C57BL/6 mice or iNOS ko mice. In untreated C57BL/6 mice, Lin-CD11b+CD115+Ly6C+ and Lin-CD11b+CD115+Ly6C- monocytes were isolated from the spleen and Lin-CD117+CD115+CD135-Ly6C+CD11b- common monocyte progenitors were isolated from the bone marrow. Myeloid-derived suppressor cells (Ly6C+CD11b+ cells derived from G-CSF, GM-CSF and IL-13 cultured C57BL/6 bone marrow) were also isolated and compared with the above populations. Lin-CD11b+CD34+ spleen cells derived from G-CSF-treated C57BL/6 mice were cultured for 3 days in Flt3 ligand and SCF and then compared to the original input population.

2015-04-01 | E-GEOD-65670 | biostudies-arrayexpress

Expression data from sorted monoyctes/macrophages

Project description:Tissue injury, such as incisional wound, results in an inflammatory response as well as acute to chronic mechanical and thermal pain. It is now understood that there is a strong contribution of these immune cells to the pain phenotype. We used microarray analysis of sorted CD11b+Ly6G- myeloid cells extracted from the mouse hindpaw 24h after incisional wound to identify distinct classes of upregulated genes. CD11b+Ly6G- myeloid cells were sorted by expression of Ly6C (high, medium, and low) and used for microarray analysis. All sorted cells were collected on the same day to reduce variability.

2015-11-06 | E-GEOD-73667 | biostudies-arrayexpress

RNA sequencing of BM myeloid cells treated with AAV-IL-27/ctrl in vivo

Project description:Interleukin-27 (IL-27) is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells and has a potential to be used as a therapeutic for cancer. We have recently demonstrated that systemic delivery of IL-27 using adeno-associated virus (AAV-IL-27) exhibits potent inhibition of tumor growth in mouse models. In this work, we demonstrate that AAV-IL-27 treatment leads to significant expansion of CD11b+Gr1+ myeloid cells (MCs). AAV-IL-27-induced expansion of CD11b+Gr1+ cells is IL-27R-dependent, requires Stat3 signaling but is inhibited by Stat1 signaling. AAV-IL-27 treatment does not increase the self-renewal capacity of CD11b+Gr1+ cells but induces significant expansion of hematopoietic stem cells (HSCs) and granulocyte-monocyte progenitor (GMP) cells. IL-27-induced Ly6G+ MCs upregulate MHC class I/II molecules but are less immune suppressive in vitro, and their expansion does not promote, but rather inhibit tumor growth in vivo. In the tumor microenvironment, IL-27 gene therapy appears to promote Ly6G+ MCs to differentiate into MHC class I/IIhigh and F4/80high macrophages. Thus, IL-27 gene therapy induces expansion of CD11b+Gr1+ myeloid cells and promotes their differentiation into anti-tumor M1 macrophages in tumor microenvironment.Bone marrow myeloid cells of tumor-bearing C57BL/6 mice treated with AAV-IL-27/ctrl for 2 weeks were sepreated by MACS. Transcriptome profiling (RNA-seq) of these purified Ly6G+ cells (>95%) was completed by BGI. Changing in gene express profiling resulted by IL-27 was analyzed in this study.

2024-03-09 | GSE227476 | GEO

Ly6C monocyte subsets transcriptome analysis from wild type and hyperhomocysteinemic mice

Project description:Murine monocytes (MC) are classified into Ly6Chigh and Ly6Clow MC. Ly6Chigh MC is the pro-inflammatory subset and the counterpart of human CD14++CD16+ intermediate MC which contributes to systemic and tissue inflammation in various metabolic disorders, including hyperhomocysteinemia (HHcy). This study aims to explore molecule signaling mediating MC subset differentiation in HHcy and control mice.Mouse white blood cell were prepared from peripheral blood and stained with antibody against CD11b, Ly6G and Ly6C and subjected for flow cytometry cell sorting. CD11b+Ly6G- cells were selected as MC. MC subsets (CD11b+Ly6G-Ly6Chigh, and CD11b+Ly6G-Ly6Clow) were sorted based on Ly6C levels. The quantification of MC was used flow cytometry analysis for Ly6Chigh and Ly6Clow MC in CT and Cbs-/-. Then, 100 ng mRNA were obtained from 100,000 sorted cells of CT and Cbs-/- (HHcy) mice. Around 30 million reads were achived and 16,487 normalized genes per sample by mRNA-Seq analysis.

2021-02-02 | GSE165879 | GEO

RNA-sequencing on sorted tumor-associated macrophages from vehicle or JHU083 pro-drug of 6-Diazo-5-oxo-L-norleucine (glutamine antagonist) treated 4T1 (breast cancer) tumor bearing mice

Project description:RNA-sequencing was performed on sorted tumor-associated macrophages (CD45+7AAD-CD11b+F4/80+CD8-Ly6C-Ly6G-) from 4T1 tumor (murine breast cancer) bearig mice with or without JHU083, pro-drug of 6-Diazo-5-oxo-L-norleucine (glutamine antagonist) treatment for expression profiling

2020-07-08 | GSE119733 | GEO

Quantitative Temporal in vivo Proteomics (QTiPs) deciphers the transition of inflammatory CD11b+,Ly6G-,Ly6Chigh myeloid cells into M2-like macrophages

Project description:Phenotypic transition of myeloid cells into distinct lineages in vivo is important in pathogen response. To monitor immune cell phenotype transitions in vivo, we developed a quantitative temporal in vivo proteomics (QTiPs) platform, performing multiplexed (10-plex) tandem-mass-tag (TMT)-based mass spectrometry on sorted cells collected from their in situ microenvironment during infection. We temporally characterized a poorly understood, virus-driven CD11b+,Ly6G-,Ly6Chigh-low myeloid cell population throughout an acute phase of infection in both the site of infection and bone marrow. QTiPs, in combination with phenotypic, functional and metabolic analyses, elucidated a pivotal role for inflammatory CD11b+,Ly6G-,Ly6Chigh-low cells in anti-viral immune response and viral clearance. Most importantly, the highly time-resolved QTiPs dataset showed the transition of CD11b+,Ly6G-,Ly6Chigh-low cells into M2-like macrophages which displayed increased antigen presentation capacities and bioenergetic demands late in infection. Our QTiPs approach precisely captures myeloid cell-macrophage transition in this population, and it is a novel platform for measuring temporospatial proteome transitions in vivo.

2017-08-09 | PXD005064 | Pride

Expression data from granulocytic MDSC (G-MDSC) and neutrophils

Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray G-MDSC (CD11b+Ly6G+Ly6Clow) were purifed from splenocytes in EL4 lymphoma tumor bearing mice by positive selection of Ly6G using microbeads isolation. Neutrophils were purified from ascitic fluids induced after injection of milk protein, casein by negative selection of F4/80 and positive selection of Ly6G using microbeads isolation. Their RNA was extracted and gene expression was analyzed using Affymetrix microarray.

2011-03-10 | E-GEOD-24102 | biostudies-arrayexpress

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