Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Programmed cell death-1 receptor mediated regulation of Tbet+NK1.1- Innate Lymphoid Cells Within the Tumor Microenvironment

ABSTRACT: Innate Lymphoid Cells (ILCs) play a key role in tissue mediated immunity and can be controlled by co-receptor signaling. Here we define a subset of ILCs that are Tbet+NK1.1- and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet+NK1.1-ILCs. PD-1 significantly controlled the proliferation and function of Tbet+NK1.1-ILCs in multiple murine and human tumors. We found tumor derived lactate enhanced PD-1 expression on Tbet+NK1.1-ILCs within the TME, which resulted in dampened mTOR signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1 deficient Tbet+NK1.1-ILCs expressed significantly increased IFNg, granzyme B and K. Furthermore, PD-1 deficient Tbet+NK1.1- ILCs contributed towards diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate anti-tumor responses of Tbet+NK1.1-ILCs within the tumor microenvironment.

ORGANISM(S): Mus musculus

PROVIDER: GSE229288 | GEO | 2023/04/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tbet-Eomes

Project description:Tbet-Eomes

| PRJNA706657 | ENA

Expression data from Tbet+ and Tbet- Memory B cells

Project description:The role of antibody and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. Here we demonstrate that B cell specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells not only controlled IgG2a production, but also mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a since T-bet in B cells was imÂportant even in the presence of virus-specific IgG2a. Our data supports a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages. NaÃ¯ve, Tbet+, and Tbet- Memory B cells were assayed for gene expression Tbet GFP reporter mice were infected with LCMV clone 13, and target B cell populations were sorted from splenocytes at day 10 post-infection

2016-08-01 | E-GEOD-81189 | biostudies-arrayexpress

Effects of durvalumab alone or combined with tremelimumab on preexisting cells in the tumor microenvironment

Project description:Immune checkpoint blockade with anti–PD-1/L1 or anti–CTLA-4 therapies has shown promising results across multiple cancer types, but the mechanisms within the tumor microenvironment (TME) have not been fully characterized. We used single-cell RNA sequencing to investigate the effects of anti–PD-L1 monoclonal antibody (mAb) durvalumab (D) alone and combined with an anti–CTLA-4 mAb, tremelimumab (T), on distinct subsets of immune cells. Upon treatment with D or D+T, two NSCLC tumors showed elevated IFNγ responses, although they differed in magnitude of response but differed in other areas. Our results highlight that D and D+T in the TME have some consistent effects across tumors but also exhibit tumor-specific effects depending on composition and functional state of immune cells in the TME at time of treatment. This complex tumor-specific interplay of diverse immune subtypes in the TME is critical to better understand patient response to immunotherapy.

2021-09-01 | GSE131933 | GEO

Cutting Edge: IL-4, IL-21, and IFN-g Interact to Govern TBET and CD11c Expression in TLR-Activated B Cells

Project description:T-Box Expressed in T cells (TBET) and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing TBET and CD11c expression remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-g that regulates TBET expression in B cells. We find that IL-21 or IFN-g directly promote TBET+ expression in the context of TLR engagement. Further, IL-4 antagonizes TBET induction. Finally, IL-21, but not IFN-g, promotes CD11c expression independent of TBET. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether TBET+ and CD11c+ B cells are formed. These findings suggest that TBET+ B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.

2016-01-23 | GSE77145 | GEO

IL-33 provision by reprogrammed tumor fibroblastic stromal cells promotes local T cell activity and facilitates melanoma eradication

Project description:The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.

2021-07-03 | E-MTAB-9407 | biostudies-arrayexpress

Tbet regulates the accessible chromatin of Be1 B cells

Project description:To investigate the role of Tbet in B cell differentiation to "effector-like" antibody secreting cells (ASC's) we utilized an ex vivo culture system to differentiate B cells in the presence of Th1 (Be1) or Th2 (Be2) polarized T cells. To determine the role of Tbet in Be1 cell differentiation we performed ATAC-seq on Wt Be1 and Tbet negative (TbetNeg) Be1 cells and Wt Be2 and Tbet negative (TbetNeg) Be2 cells. Collectively, these data show that T-bet serves as master regulator for the Be1 cell fate and is required to program chromatin accessibility during ASC differentiation in Be1 cells.

2019-04-29 | GSE118984 | GEO

Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma

Project description:Anti-PD-1 immunotherapies have transformed cancer treatment, but the determinants of clinical response are largely unknown. We performed CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions of advanced cutaneous T cell lymphoma (CTCL) from 14 patients enrolled in a clinical trial of pembrolizumab therapy. Clinical response was not associated with the frequency of tumor-infiltrating T cell subsets, but rather with striking differences in the spatial organization and functional immune state of the tumor microenvironment (TME). After treatment, pembrolizumab responders had a localized enrichment of tumor and CD4+ T cells, which coincided with immune activation and cytotoxic PD-1+ CD4+ T cells. In contrast, non-responders had a localized enrichment of Tregs pre- and post-treatment, consistent with a persistently immunosuppressed TME and exhausted PD-1+ CD4+ T cells. Integrating these findings by computing the physical distances between PD-1+ CD4+ T cells, tumor cells, and Tregs revealed a spatial biomarker predictive of pembrolizumab response. Finally, the chemokine CXCL13 was upregulated in tumor cells in responders post-treatment, suggesting that chemoattraction of PD-1+ CD4+ T cells towards tumor cells facilitates a positive outcome. Together, these data show that T cell topography reflects the balance of effector and suppressive activity within the TME and predicts clinical response to PD-1 blockade in CTCL.

2021-09-17 | GSE162137 | GEO

Kinetics of Tbet+ B cells during LCMV infection

Project description:Inflammatory (B220+ CD19+ CD44+ CD11c+ Tbet-AmCyanhi) B cells were sorted from female Tbet-AmCyan reporter mice at day 8, 10, and 15 post infection with LCMV-Armstrong. RNA-seq was employed to assess transcriptional changes in inflammatory B cells throughout the infection.

2022-01-27 | GSE192765 | GEO

Kinetics of Tbet+ B cells during LCMV infection

2022-01-27 | GSE150139 | GEO

Tbet vs Eomes [RNA-Seq]

Project description:T-bet and Eomes are related T-box transcription factors that control NK cell development. This study was designed to understand the specific roles of Eomes and T-bet in regulating gene expression. RNAseq data were generated for immature (CD11b- CD27+) and mature (CD11b+ CD27-) NK cells from T-bet KO (Tbet Ho) or control mice (Tbet WT) or from Eomes KO (Eomes Ho) or control mice (NK-Cre). Three samples were generated for each condition (Tri 1, 2, 3).

2021-05-10 | GSE168240 | 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