Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1091459 | ENA |
REPOSITORIES: ENA
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Project description:Immunophenotyping of tumor microenvironment (TME) is crucial for immunotherapy efficacy in patients with solid tumours. However, strategies to characterize TME are largely limited with huge heterogeneity. We show that endoplasmic reticular oxidoreductase-1α (ERO1A) induces an immune-suppressive TME and resistance to PD-1 blockade by promoting endoplasmic reticulum (ER) stress response. Single-cell RNA sequencing analyses confirm that ERO1A is correlated with immunosuppression and dysfunction of CD8+ T cell along anti-PD-1 treatment. Ablation of Ero1a in tumours promotes the infiltration of lymphocytes as well as cytotoxicity of CD8+ T cells and enhances response to anti-PD-1 treatment in mouse models.
2023-08-13 | GSE224525 | GEO
Project description:Pancreatic cancer liver metastasis (PCLM) is an important factor leading to dismal prognosis. The adaptive remodeling of the tumor microenvironment (TME), especially the role of neutrophil in liver metastasis remains elusive. Here we combined single-cell sequencing combined with spatial transcriptomics on patients’ samples to characterize the landscape of PCLM, and explored the functional diversity possessed by neutrophils infiltrated in liver metastases. We identified the pivotal Neutrophils_S100A12 cluster capable of promoting metastatic progression by releasing neutrophil extracellular traps (NETs); spatially, Neutrophils_S100A12 cells are specifically distributed at the invasive front of the metastatic lesions. Mechanistically metastatic TME activates canonical TGF-β/SMAD3 signaling within neutrophil, resulting in NFE2-mediated phenotypic polarization; furthermore NFE2 induces NETs generation by up-regulating PADI4 expression. Interference with NFE2 activation in neutrophils prevents phenotypic conversion and reduces liver metastasis. Our data demonstrate that NFE2-mediated neutrophil polarization in PCLM is a potential target for anti-metastatic therapy.
2025-01-18 | GSE281288 | GEO
Project description:In addition to the tumour cells, breast tumours contain other cell types such as fibroblasts, adipocytes, inflammatory and immune cells. Together with the extracellular matrix, these non-tumour cells compose the tumour microenvironment (TME). Complex interactions occur between tumour cells and the TME that can inhibit or stimulate tumour cell growth, metastasis and/or chemoresistance. While treatment of tumours with chemotherapeutic agents such as Abraxane, leads to apoptosis of tumour cells, it can also have consequences for the cellular makeup and transcriptional profile of the TME and these, like the increased infiltration of macrophages, may have detrimental effects. Transcriptome profiling of whole tumours from mice injected with tumour cell lines and treated with combinations of chemotherapeutic drugs has provided novel insights into pathways affected by different agents and diagnostic signatures. However, differences in the cellular composition of tumours from treated mice can have confounding effects and increase variation in whole tumour transcriptomes. To be able to examine the effects of co-treatment of Abraxane with another drug, we performed RNA-seq on tumours from mice injected with the human breast cancer cell line MDA-MB-231. We then separated reads mapped to the human and mouse genomes in silico, creating tumour and TME transcriptomes for control, Abraxane, drug and combination treated mice. Separation of the tumour and TME profiles revealed that while in the tumour cells, co-addition of the drug potentiated Abraxane’s inhibitory effect on cell cycle genes and promotional effect on antigen presentation genes, in the TME it inhibited genes involved in the inflammation and migration responses and promoted genes involved in lipid and xenobiotic metabolism.
2020-10-01 | GSE121119 | GEO
Project description:The breast tumour microenvironment (TME) includes fibroblasts, adipocytes, inflammatory and immune cells. While treatment of tumours with chemotherapeutic agents such as Docetaxel, leads to apoptosis of tumour cells, it can also have consequences for the cellular makeup and transcriptional profile of the TME and these, like increased epithelial mesenchymal transition can promote undesirable consequences, such as Cancer Stem Cell development. PKC-theta may have a role in these undesired effects. To be able to examine the effects of co-treatment of Docetaxel with an inhibitor of PKC-theta, we performed RNA-seq on tumours from mice injected with the human breast cancer cell line MDA-MB-231. We then separated reads mapped to the human and mouse genomes in silico, creating tumour and TME transcriptomes for control, Docetaxel, PKC-theta inhibitor and combination treated mice. Separation of the tumour and TME profiles illustrated a role for PKC-theta in the induction of a more basal-type transcriptome in the tumour, and of EMT in the TME.
2022-09-14 | GSE137467 | GEO
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
Project description:Comparing two agonists of interleukin-2 (IL-2), IL-2wt and IL-2nα, differentially reshape the tumor microenvironment (TME). To more comprehensively explore the mechanisms by which the two different IL-2R agonists regulate the TME, we performed single-cell RNA sequencing (scRNA-seq) on immune cells isolated from tumors. We clustered the 18,455 tumor-infiltrating immune cells into 5 populations, and found marked expansion of T cell populations as well as contraction of mononuclear phagocyte populations in both IL-2wt and IL-2nα treated tumors compared with immunoglobulin G (IgG) controls.
2023-04-02 | E-MTAB-12373 | biostudies-arrayexpress
Project description:Transcriptome profiles of C3H/HeJ mouse liver tumours
| PRJEB27617 | ENA
Project description:Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.
2023-09-30 | E-MTAB-13322 | biostudies-arrayexpress
Project description:Mouse tumour organoids (MTOs) derived from a compound mutant (LAKTP) intestinal cancer model were orthoptopically transplanted into syngeneic C57BL/6J mice. Tumour-bearing mice were treated with TGF-beta inhibitor Galunisertib or vehicle control. Whole tumour mRNA was extracted from primary tumours and expression profiling was performed with the objective to characterize the tumour microenvironment (TME). As a TGF-beta-activated TME has been associated to a poor prognosis and the CRC consensum molecular subtype CMS4, and the mouse model was found to have such an activated TME, we used the array data to classify these tumours in this mouse model system as CMS4-like. Furthermore, treatment with TGF-beta inhibitor reduced the fibroblast- and T cell-specific TGF-beta response signatures, also associated to poor prognosis in human CRC. This treatment was associated to a strong reduction/prevention of liver metastasis, as well as a reduction of primary tumour (and local carcinomatosis) size.
2018-02-12 | GSE103562 | GEO