Investigation of the Effect and Target of SchA in the Treatment of Triple-Negative Breast Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE328358 | GEO | 2026/06/11
REPOSITORIES: GEO
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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
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:Following therapy, tumour-initiating cells (TICs) survive and give rise to second-line tumours. Gene set enrichment analysis of microarray data and microRNA analysis confirmed the validity of spheroid cultures as models of TICs for breast and prostate cancer and mesothelioma cell lines. Pathway analysis revealed increased Trp metabolism in all types of TICs with indoleamine 2,3-dioxygenase (IDO) as the rate-limiting enzyme. TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. Mitocans, represented by vitamin E (VE) analogues, suppressed IDO1 in TICs with functional mitochondrial complex II, a target for the agents. IDO1 expression was regulated via a mechanism involving both transcriptional and post-transcriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work points to Trp metabolism as a novel mechanism of TICs to bypass the immune surveillance and to VE analogues as agents that remove this ‘mimicry’. Total RNA obtained from from breast cancer (MCF7), mesothelioma (IstMes2) and prostate cancer (LNCaP) adherent cell lines was compared to their corresponding sphere cultures
2013-11-01 | E-GEOD-41980 | biostudies-arrayexpress
Project description:This study aimed to identify the mode of action of Schisandra chinensis water extracts (SCW) and Schisandra chinensis ethanol extracts (SCE) in SW1783 cell line.
2025-05-19 | GSE294592 | GEO
Project description:Following therapy, tumour-initiating cells (TICs) survive and give rise to second-line tumours. Gene set enrichment analysis of microarray data and microRNA analysis confirmed the validity of spheroid cultures as models of TICs for breast and prostate cancer and mesothelioma cell lines. Pathway analysis revealed increased Trp metabolism in all types of TICs with indoleamine 2,3-dioxygenase (IDO) as the rate-limiting enzyme. TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. Mitocans, represented by vitamin E (VE) analogues, suppressed IDO1 in TICs with functional mitochondrial complex II, a target for the agents. IDO1 expression was regulated via a mechanism involving both transcriptional and post-transcriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work points to Trp metabolism as a novel mechanism of TICs to bypass the immune surveillance and to VE analogues as agents that remove this ‘mimicry’.
2013-11-01 | GSE41980 | GEO
Project description:Kynurenine, an intermediate metabolite of tryptophan metabolism, suppresses the antitumor activity of CD8+ T cells by activating the aryl hydrocarbon receptor (AHR). Its role in adaptive immunity is poorly understood. Outside the liver, kynurenine is mainly produced by indoleamine 2,3-dioxygenase 1 (IDO1) and further degraded by kynureninase (KYNU). This report shows that KYNU is predominantly expressed in human and mouse antigen-presenting cells (APCs) in vivo, GM-CSF-differentiated macrophages and dendritic cells in vitro, and alveolar macrophages collected in situ, and is functionally active in breaking down kynurenine into catabolic products without contributing towards de novo NAD+ synthesis. Importantly, while CD8+ T cells uptake kynurenine, they lack active KYNU, leading to AHR-dependent immunosuppression. However, KYNU-expressing APCs can deplete extracellular kynurenine, prevent AHR activation, and restore IFNγ production in CD8+ T cells. This highlights the importance of KYNU-expressing APCs in combating kynurenine-induced immune suppression against tumors.
2026-02-23 | PXD074605 | Pride
Project description:Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) has also immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient (Ido1-/-) BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with Ido1-/- BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) alloBMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and IL-10, Ido1-/- Gr1+CD11b+ cells from allo-BMT or in vitro BM culture showed compromised immunesuppressive functions and were skewed toward the Ly6ClowLy6Ghi subset, compared with the WT counterparts. Importantly, Ido1-/-Gr-1+CD11b+ cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities, and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by Nacetylcysteine reverted the Ido1-/-Gr-1+CD11b+ composition and function to an MDSC state, as well as improved the survival of GVHD hosts with Ido1-/- BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr1+CD11b+ MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a novel mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1.
2021-12-20 | GSE163730 | 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:Sepsis triggers a systemic inflammatory response that leads to immune dysregulation and widespread organ damage. Acute thymic involution (ATI), a hallmark of sepsis, is characterized by decreased T cell production and weakened immune responses. The mechanism of ATI is not fully understood. In this study, we demonstrate that ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in ATI during sepsis. Using a polymicrobial sepsis model, we observed significant ferroptosis-associated thymic damage, which was marked by lipid peroxidation, mitochondrial dysfunction, and a reduction in thymic size and cellularity. Treatment with 1-methyltryptophan (1-MT), an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), effectively reversed these phenotypes, restoring thymic structure and function, and significantly improved survival outcomes in septic mice. Further mechanistic analysis revealed that IDO1 upregulation led to the accumulation of kynurenine, which activates the aryl hydrocarbon receptor (AhR), thereby driving ferroptosis in thymocytes. Our findings uncover a novel role for the IDO1/Kyn/AhR pathway in ferroptosis and suggest that targeting this pathway could be a promising therapeutic strategy for restoring thymic function and improving outcomes in sepsis.
2025-07-30 | GSE280678 | GEO
Project description:Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome but the cellular and molecular niches that facilitate IC expression during leishmaniasis are ill-defined. We previously showed that in Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesion skin and that reduced PD-L1 expression early after treatment onset predicted cure rate following antimonial therapy. Here, we use spatial cell interaction mapping to identify IL-32-expressing CD8+ memory cells and regulatory T cells as key components of the IDO1 / PD-L1 niche in Sri Lankan CL patients and in patients with distinct forms of dermal leishmaniasis in Brazil and India. Furthermore, the abundance of IL-32+ cells and IL-32+CD8+ T cells at treatment onset was prognostic for rate of cure in Sri Lankan patients. This study provides a unique spatial perspective on the mechanisms underpinning IC expression during CL and a novel route to identify additional biomarkers of treatment response.
2025-02-20 | GSE290027 | GEO