Single Cell RNAseq of blood and tumor from renal cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001004230 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Longitudinal phenotyping of T cells and myeloid cells in early (day 14) and late (day26) GL261 tumors. Single cell RNA sequencing of CD45+ immune cell from intracranial murine GL261-SIINFEKL tumors 20 days after inoculation. SIINFEKL-reactive T cells were sorted based on dextramer staining. Using time-resolved scRNA-seq of murine tumor-infiltrating immune cells from early (d14) and late stage (d26) syngeneic GL261 gliomas we observed constant MHCII expression by murine microglia over time and overall high but decreasing MHCII expression in late stage bbm indicating a dynamic process of MHCII expression. We show that loss of major histocompatibility complex (MHC) class II (MHCII)-restricted antigen presentation on bbm drives dysfunctional intratumoral tumor-reactive CD8+ T cell states through increased expression of Tox, a critical regulator of T cell exhaustion. By calculating the normalized abundance of T cell states along the pseudotime trajectory of SIINFEKL-reactive CD8+ T cells retrieved from myeloidMHCII-proficient and -deficient microenvironments, we found an enrichment of a distinct T cell state in myeloidMHCIIKO CD8+ T cells that was defined by peak expression of exhaustion markers. Mechanistically, MHCII-dependent activation of CD4+ T cells restricts myeloid-derived osteopontin that triggers a chronic activation of nuclear factor of activated T cells (Nfat)2 in tumor-reactive CD8+ T cells. In summary, we provide evidence that MHCII-restricted antigen presentation on bbm is a key mechanism to directly maintain functional cytotoxic T cell states in brain tumors.
2023-01-19 | E-MTAB-12523 | biostudies-arrayexpress
Project description:Single cell ATAC sequencing of SIINFEKL-reactive immune cell from intracranial murine GL261-SIINFEKL tumors 20 days after inoculation. SIINFEKL-reactive T cells were sorted based on dextramer staining. We show that loss of major histocompatibility complex (MHC) class II (MHCII)-restricted antigen presentation on bbm drives dysfunctional intratumoral tumor-reactive CD8+ T cell states through increased chromatin accessibility and expression of Tox, a critical regulator of T cell exhaustion.
2023-01-11 | E-MTAB-12512 | biostudies-arrayexpress
Project description:Using complementary forms of high dimensional profiling we define differences in CD45+ cells from syngeneic mouse tumors that either grow progressively or eventually reject following immune checkpoint therapy (ICT). Unbiased assessment of gene expression of tumor infiltrating cells by single cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments. Surprisingly, we observed multiple subpopulations of monocytes/macrophages distinguishable by the combinatorial presence or absence of CD206, CX3CR1, CD1d and iNOS, markers of different macrophage activation states that change over time during ICT in a manner partially dependent on IFNγ. Both the CyTOF data and additional analysis of scRNAseq data support the hypothesis that macrophage polarization/activation results from effects on circulatory monocytes/early macrophages entering tumors rather than on pre-polarized mature intratumoral macrophages. Thus, ICT induces transcriptional and functional remodeling of both myeloid and lymphoid compartments.
2018-10-30 | GSE119352 | GEO
Project description:Stem cells are critical for the maintenance of many tissues, and thus their integrity is crucial, but whether this integrity is maintained in the face of an immune response is not well defined. Here we set out to determine the outcome of T cell interactions with adult stem cells in their physiological niche. We find that fast cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as ovary and mammary stem cells, are eliminated by activated T-cells, but slow cycling stem cells, specifically hair follicle and muscle stem cells, are resistant to T-cell killing. This is an intrinsic property of the quiescent stem cells resulting from systemic downregulation of the antigen presentation machinery, including MHC class I, Tap proteins, and the transactivator Nlrc5, which is reversed upon stem cell entry into the cell cycle. These findings identify a link between tissue stem cell quiescence, antigen presentation, and immune evasion, and may help explain why mutations in long-lived stem cells would not lead to immune editing. They also suggest how cancer-initiating cells may evade immune surveillance
2018-04-01 | GSE109574 | GEO
Project description:the WHSC1 enzymes controls immune infiltration in prostate cancer by regulating the expression of genes in immune pathways and genes in the antigen processng and presentation machinery
2020-12-11 | GSE153335 | GEO
Project description:the WHSC1 enzymes controls immune infiltration in prostate cancer by regulating the expression of genes in immune pathways and genes in the antigen processng and presentation machinery
2020-12-11 | GSE153333 | GEO
Project description:<p>Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. The purpose of this study was to investigate whether alterations in genes encoding components of the HLA Class I antigen processing and presentation machinery or interferon signaling pathways play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Whole exome sequencing was performed on tumor samples collected from patients with advanced non-small cell lung cancer at the time of resistance to PD-1 axis inhibitors and on available matched pre-treatment and normal samples. Patient-derived xenografts successfully established from the ICI-resistant samples were also exome sequenced. Additionally, RNA sequencing was performed on cases with sufficient tissue.</p>
| phs001464 | dbGaP
Project description:This model of the immune system response to antigen presentation is based on the publication:
Eduardo D.Sontag (2017) 'A Dynamic Model of Immune Responses to Antigen Presentation Predicts Different Regions of Tumor or Pathogen Elimination', Cell Systems, 4(2)
DOI: 10.1016/j.cels.2016.12.003
Comment:
This model is based on the "toy model" as described by Equations 1A-1C from the manuscript and the system represented by Equation 2, which exhibits a type of incoherent feedforward loop (IFFL).
Abstract:
The immune system must discriminate between agents of disease and an organism’s healthy cells. While the identification of an antigen as self/non-self is critically important, the dynamic features of antigen presentation may also determine the immune system’s response. Here, we use a simple mathematical model of immune activation to explore the idea of antigen discrimination through dynamics. We propose that antigen presentation is coupled to two nodes, one regulatory and one effecting the immune response, through an incoherent feedforward loop and repressive feedback. This circuit would allow the immune system to effectively estimate the increase of antigens with respect to time, a key determinant of immune reactivity in vivo. Our model makes the prediction that tumors growing at specific rates evade the immune system despite the continuous presence of antigens indicating disease, a phenomenon closely related to clinically observed “two-zone tolerance.” Finally, we discuss a plausible biological instantiation of our circuit using combinations of regulatory and effector T cells.
2024-09-02 | BIOMD0000001030 | BioModels
Project description:Immune evasion is an important hallmark of cancer ensured by diverse strategies, including immunosuppression and downregulation of antigen presentation. Here, to restore immunogenicity of cancer cells, we employed the minimal gene regulatory network of highly immunogenic type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen presenting cells (APCs). We showed that enforced expression of PU.1, IRF8 and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 33 cell lines derived from human and mouse hematological and solid tumors. PIB gradually modified the cancer cell transcriptional and epigenetic program imposing global antigen presentation and cDC1 gene signatures within 9 days. cDC1 reprogramming restored the expression of antigen presentation complexes as well as co-stimulatory molecules at the cell surface, leading to the presentation of endogenous antigens on MHC-I, and to CD8+ T cell mediated killing. Functionally, tumor- APCs acquired the ability to uptake and process exogenous proteins and dead cells, secreted inflammatory cytokines and cross-presented antigens to naïve CD8+ T cells. Importantly, tumor-APCs were efficiently generated at the single cell level from primary cancer cells of 7 solid tumors that presented antigens to memory and naïve T-cells, as well as to activated patient-specific intra-tumoral lymphocytes. Alongside antigen presentation, tumor-APCs harboring TP53, KRAS and PTEN mutations showed impaired tumorigenicity in vitro and in vivo. Finally, using in vivo mouse models of melanoma, we showed that intra-tumoral injection of tumor-APCs promoted lymphoid infiltration, delayed tumor growth and increased survival. The anti-tumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors enabling tumor eradication. Our approach combines cDC1’s antigen processing and presenting abilities with endogenous generation of tumor antigens and serves as a platform for the development of novel immunotherapies based on endowed antigen presentation in cancer cells.
2023-10-24 | PXD039789 | Pride
Project description:mechanism of antigen presentation of avian dendritic cells
| PRJNA598803 | ENA