Identification of indoleamine 2, 3-dioxygenase 1 (IDO1) regulated genes in human glioblastoma cell line U87
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA733217 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptome analysis of U87 cells under different treatments to identify IDO1-regulated genes Indoleamine 2, 3-dioxygenase 1 (IDO1) is a tryptophan (Trp) catabolic enzyme that converts Trp into downstream kynurinine (Kyn). Many studies have indicated that IDO1 is a critical suppressive immune checkpoint molecule invovled in various types of cancer. Canonically, the underlying mechanism of IDO1 immunosuppressive role is related with its enzyme activity, that is the depletion of Trp and accumulation of Kyn lead to increased tumor infiltrating suppressive regulatory T cells. Recent studies, however, challenged this hypothesis and imply that tumor cell-derived IDO1 can mediate immunosuppression independent of its enzyme activity. In this study, we aim to identify genes that are regulated by IDO1 in human glioblastoma cells, a gene expression regulatory function of IDO1 that is indepent of its enzyme activity.
2021-12-10 | GSE175700 | GEO
Project description:Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. Hitherto, indoleamine-2,3-dioxygenase 1 (IDO1) or tryptophan- 2, 3-dioxygenase (TDO2) are recognized as the main Trp-catabolizing enzymes (TCEs) responsible for the generation of AHR agonists. Here, the ability of the aromatic L-amino acid oxidase, interleukin 4 induced 1 (IL4I1), to activate the AHR was investigated using IL4I1 knockout CAS-1 glioblastoma cells.
2020-08-19 | GSE149910 | GEO
Project description:Early acute rejection of human allografts is mediated by circulating alloreactive host effector memory T cells (TEM). TEM infiltration typically occurs across graft post-capillary venules and involves sequential interactions with graft-derived endothelial cells (ECs) and pericytes (PCs). While the role of ECs in allograft rejection has been extensively studied, contributions of PCs to this process are largely unknown. This study aimed to characterize the effects and mechanisms of interactions between human PCs and allogeneic TEM. We report that unstimulated PCs, like ECs, can directly present alloantigen to TEM but while IFN-γ-activated ECs (γ-ECs) show increased ability to stimulate alloreactive T cells, IFN-γ-activated PCs (γ-PCs) instead suppress TEM proliferation but not cytokine production or signaling. RNA sequencing analysis of PCs, γ-PCs, ECs, and γ-ECs reveal induction of indoleamine 2,3-dioxygenase 1 (IDO1) in γ-PCs to significantly higher levels than in γ-ECs that correlates with tryptophan depletion in vitro. Consistently, shRNA knockdown of IDO1 markedly reduces -PC-mediated immunoregulatory effects. Adoptively transferred T cells induced PC expression of IDO1 in allogeneic human skin grafts on immunodeficient mice. We conclude that immunosuppressive properties of human PCs are not intrinsic but instead result from IFN-γ-induced IDO1-mediated tryptophan depletion.
2018-05-09 | GSE109322 | GEO
Project description:Neutrophil granulocytes are the major cells involved in the Chlamydia trachomatis (C.trachomatis)-mediated inflammation and histopathology. A key gene in human intracellular antichlamydial defense is the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO), which limits the growth of the tryptophan auxotroph Chlamydia. Despite its importance, the role of IDO in the intracellular defense against Chlamydia in neutrophils has not yet been characterized. Affymetrix microarrays were used to obtain global gene expression data for monitoring the effect of C. trachomatis serovar D infection on the transcriptome of human neutrophil granulocytes.
2021-11-08 | GSE180238 | GEO
Project description:CD40-stimulating immunotherapy elicits potent anti-tumor responses, which are mainly T-cell dependent. Here, we have investigated how tumor endothelial cells respond to CD40-stimulating immunotherapy by isolating endothelial cells from B16.F10 melanoma in anti-CD40 treated or isotype treated mice followed by RNA-sequencing. Gene set enrichment analysis revealed an increase in interferon- related responses in tumor endothelial cells following anti-CD40 therapy. The immunosuppressive enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) was preferentially expressed in endothelial cells, and it was up-regulated upon anti-CD40 treatment. IDO1 expression in tumor endothelium was positively correlated to T-cell infiltration and to increased expression of IFNγ in the tumor microenvironment. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFNγ, but not in response to CD40-stimulation. Combining agonistic anti-CD40 therapy with the IDO1 inhibitor epacadostat delayed tumor growth and increased survival in B16.F10 tumor-bearing mice, which was associated with increased activation of tumor-infiltrating T-cells. Hereby, we have uncovered an immunosuppressive feedback mechanism, in which tumor vessels limit the efficacy of cancer immunotherapy by up-regulating IDO1 in response to T-cell activation.
2020-04-06 | GSE130679 | GEO
Project description:Indoleamine 2, 3-dioxygenase 1 (IDO1) is a metabolic enzyme catalyzing the conversion of the essential amino acid tryptophan to kynurenine. It is induced by IFNg and its expression is linked to poor prognosis across various cancer types. T cells are particularly sensitive to IDO1-dependent tryptophan deprivation in the tumor microenvironment, leading to tumor immune resistance. Therefore, IDO1 inhibitors, such as epacadostat, have been developed, aiming to restore T cell antitumor activity. However, a recent phase III trial assessing the clinical benefit of epacadostat with the PD-1 antibody pembrolizumab in melanoma failed. This prompted us to study the role of IDO1, and the effect of its inhibition, on tumor cells that are under IFNg treatment and T cell attack. We showed that IDO1-mediated tryptophan depletion contributes to the anti-tumor effect of CD8 T cells. Thus, while epacadostat expectedly replenished tryptophan -the desired effect-, this led to adverse protection of melanoma cells from T cell-derived IFNg. RNA sequencing and ribosome profiling of (patient-derived) melanoma cell lines revealed that IFNg caused general protein translation shut down, which was reversed by IDO1 inhibition. Impaired translation was accompanied by an amino acid deprivation-dependent stress response driving ATF4high and MITFlow transcriptomic signatures, which was also observed in melanoma patient tumors. Downregulation of MITF in tumors and PDX- derived cell lines upon treatment was strongly predictive of response to response, to checkpoint blockade-treatment and IFNg, respectively. Conversely, MITF restoration in cultured tumor cells caused T cell resistance. These results highlight the critical role of tryptophan in the melanoma response to T cell-derived IFNg, uncovering an unexpected negative consequence of IDO1 inhibition.
2023-01-16 | GSE198460 | GEO
Project description:Dendritic cells (DCs) are pivotal drivers of anti-tumor immunity, but many of the DCs in tumors appear dysfunctional or immunosuppressive. Using mouse models, we found that robustly immunogenic DCs can arise by differentiation from immature myeloid precursor cells during inflammation. In tumors, however, differentiation of these inflammatory DCs was blocked by a cell-intrinsic signaling pathway created by Bruton’s Tyrosine Kinase (BTK) and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO).
2021-08-25 | GSE180038 | GEO
Project description:Dendritic cells (DCs) are pivotal drivers of anti-tumor immunity, but many of the DCs in tumors appear dysfunctional or immunosuppressive. Using mouse models, we found that robustly immunogenic DCs can arise by differentiation from immature myeloid precursor cells during inflammation. In tumors, however, differentiation of these inflammatory DCs was blocked by a cell-intrinsic signaling pathway created by Bruton’s Tyrosine Kinase (BTK) and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO).
2021-08-25 | GSE180026 | GEO
Project description:After performing an in-vivo screening with U87 glioblastoma cells transduced with a knockdown library several genes could be identified. Lin7a which was one of the candidates was further evaluated. Single knockdown of Lin7a in U87 conferred a pro-invasive phenotype in-vitro and in-vivo. Overexpression of Lin7a in the Primary glioblastoma cell line T269 reduced its invasive phenotype. To decipher the underlying pathways U87 control, U87-shLIN7a and U87-shLin7a+Lin7A (rescue cells after re-expression of Lin7A) were analyzed after in-vitro culture by a transcription profiling Array.
2017-08-27 | E-MTAB-5871 | biostudies-arrayexpress
Project description:The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated STAT1 functions in intestinal tumorigenesis of ApcMin mice. Surprisingly, loss of STAT1 in intestinal epithelial cells (STAT1ΔIEC) interfered with ApcMin induced intestinal tumor formation and tumor progression. RNASeq data demonstrated reduced expression of Indoleamine-2,3-dioxygenase-1 (IDO1) in STAT1ΔIEC ApcMin tumors. IDO1 is implicated in synthesis of kynurenine, a metabolite that induces ß-Catenin nuclear localisation and suppresses anti-tumor immune responses.
2020-04-05 | E-MTAB-5083 | biostudies-arrayexpress