Parkin activation suppresses antigen presentation of macrophages to promote tumour progression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1006436 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25684731_1.fastq.gz | Fastqsanger.gz | |||
| SRR25684731_2.fastq.gz | Fastqsanger.gz | |||
| SRR25684732_1.fastq.gz | Fastqsanger.gz | |||
| SRR25684732_2.fastq.gz | Fastqsanger.gz | |||
| SRR25684733_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Here, through a series of in vivo murine tumour progression models, we found that Parkin deficiency inhibit the progression of multiple cancers. scRNA-seq analyses were performed on tumour-infiltrating CD45+ cells sorting from MC38 tumours in WT or Park2-/- mice. scRNA-seq and flow cytometry analyses profiled distinct anti-tumour macrophage subsets and effector T cell subsets in the tumor immune microenvironment of Park2-/- mice, which were further validated by adoptive transfer assays. Mechanistically, Parkin deficiency facilitates MHC-I expression on TAMs through an unconventional AMPK-dependent pathway, thereby yielding antigen-specific T-cell activation and persistent tumoricidal effects. In addition, we found that Park2-/- TAMs-related signature was associated with improved prognosis in solid tumour patients. Our findings underscore Parkin as a negative immune regulator confining intercellular crosstalk between macrophages and T cells that underpins tumour immune evasion, reinforcing Parkin as a promising target for optimizing tumour immunotherapy.
2025-03-21 | GSE241129 | GEO
Project description:Oligomeric human Aβ1-42 inhibits antigen presentation
| PRJNA563674 | ENA
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity. Comparison of murine mannose receptor negative versus mannose receptor positive bone marrow-derived DCs
2010-05-08 | E-GEOD-15616 | biostudies-arrayexpress
Project description:A key unknown of the functional space in tumor immunity is whether physiologically relevant cancer antigen presentation occurs solely in draining lymph nodes versus tumors. Professional antigen presenting cells, i.e. the dendritic cells, are scarce and immature within tumors, greatly outnumbered by MHCII expressing non-hematopoietic cells, such as antigen-presenting cancer-associated fibroblasts (apCAFs). We hypothesized that after their exit from tumor-draining lymph nodes T cells depend on a second wave of antigen presentation provided in situ by structural cells. We show that dense apCAF regions in human lung tumors define hot immunological spots with increased numbers of CD4 T cells. The transcriptomic profile of human lung apCAFs aligned to that of pancreatic apCAFs across mice and humans and were both enriched for alveolar type II genes, suggesting an epithelial origin. Mechanistically, human apCAFs directly activated the TCRs of adjacent effector CD4 T cells and at the same time produced high levels of c1q, which acted on surface c1qbp on T cells to rescue them from apoptosis. Fibroblast-specific deletion of MHCII in mice impaired local MHCII immunity and accelerated tumor growth, while inducing c1qbp overexpression in adoptively transferred T cells expanded their numbers within tumors and reduced tumour burden. Collectively, our work shows that tumor T cell immunity post lymph node exit requires peripheral antigen presentation by a subset of CAFs and proposes a new conceptual framework upon which effective cancer immunotherapies can be built.
2021-12-13 | GSE164653 | GEO
Project description:A key unknown of the functional space in tumor immunity is whether physiologically relevant cancer antigen presentation occurs solely in draining lymph nodes versus tumors. Professional antigen presenting cells, i.e. the dendritic cells, are scarce and immature within tumors, greatly outnumbered by MHCII expressing non-hematopoietic cells, such as antigen-presenting cancer-associated fibroblasts (apCAFs). We hypothesized that after their exit from tumor-draining lymph nodes T cells depend on a second wave of antigen presentation provided in situ by structural cells. We show that dense apCAF regions in human lung tumors define hot immunological spots with increased numbers of CD4 T cells. The transcriptomic profile of human lung apCAFs aligned to that of pancreatic apCAFs across mice and humans and were both enriched for alveolar type II genes, suggesting an epithelial origin. Mechanistically, human apCAFs directly activated the TCRs of adjacent effector CD4 T cells and at the same time produced high levels of c1q, which acted on surface c1qbp on T cells to rescue them from apoptosis. Fibroblast-specific deletion of MHCII in mice impaired local MHCII immunity and accelerated tumor growth, while inducing c1qbp overexpression in adoptively transferred T cells expanded their numbers within tumors and reduced tumour burden. Collectively, our work shows that tumor T cell immunity post lymph node exit requires peripheral antigen presentation by a subset of CAFs and proposes a new conceptual framework upon which effective cancer immunotherapies can be built.
2021-12-13 | GSE164659 | GEO
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity.
2009-06-19 | GSE15616 | GEO
Project description:Parkin is an E3 ubiquitin ligase, which plays a key role in the development of Parkinson disease. Parkin defects also occur in numerous cancers, and a growing body of evidence indicates that Parkin functions as a tumor suppressor that impedes a number of cellular processes involved in tumorigenesis. Here, we generated murine and human models that closely mimic the advanced-stage tumors where Parkin deficiencies are found to provide deeper insights into the tumor suppressive functions of Parkin. Loss of Parkin expression led to aggressive tumor growth, which was associated with poor tumor antigen presentation and limited antitumor CD8+ T-cell infiltration and activation. The effect of Parkin deficiency on tumor growth was lost following depletion of CD8+ T cells. In line with previous findings, Parkin deficiency was linked with mitochondria-associated metabolic stress, PTEN degradation, and enhanced Akt activation. Increased Akt signaling led to dysregulation of antigen presentation, and treatment with the Akt inhibitor MK2206-2HCl restored antigen presentation in Parkin-deficient tumors. Analysis of data from patients with clear cell renal cell carcinoma indicated that Parkin expression was downregulated in tumors and that low expression correlated with reduced overall survival. Furthermore, low Parkin expression correlated with reduced patient response to immunotherapy. Overall, these results identify a role for Parkin deficiency in promoting tumor immune evasion that may explain the poor prognosis associated with loss of Parkin across multiple types of cancer.SignificanceParkin prevents immune evasion by regulating tumor antigen processing and presentation through the PTEN/Akt network, which has important implications for immunotherapy treatments in patients with Parkin-deficient tumors.
| S-EPMC10618737 | biostudies-literature
Project description:p53 suppresses MHC class II antigen presentation by the intestinal epithelium to protect intestinal stem cells upon radiation
| PRJNA940152 | ENA
Project description:Current cancer immunotherapies are assumed to improve infiltration and cytotoxicity of immune cells in the tumor. However, tumor cells have developed a variety of resistance mechanisms to suppress the MHC class I antigen presentation, and thereby impair the cytotoxicity of CD8+ T cells. Here, we identified Mal2 as a key player that mediates the turnover of the antigen-MHC-I complex and reduce the antigen presentation on tumor cells. Mal2 promotes the endocytosis of tumor antigen via direct interaction with the MHC-I complex and endosome-associated Rab5/7. In mouse and human breast tumor models, inhibition of Mal2 profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that Mal2 is a potential target for breast cancer immunotherapy.
2020-01-23 | GSE144099 | GEO
Project description:Modelling of anti-tumour immune response: Immunocorrective effect
of weak centimetre electromagnetic waves
O.G. Isaeva* and V.A. Osipov
Bogoliubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, Dubna,
Moscow Region, Russia
We formulate the dynamical model for the anti-tumour immune response based on
intercellular cytokine-mediated interactions with the interleukin-2 (IL-2) taken into
account. The analysis shows that the expression level of tumour antigens on antigen
presenting cells has a distinct influence on the tumour dynamics. At low antigen
presentation, a progressive tumour growth takes place to the highest possible value.
At high antigen presentation, there is a decrease in tumour size to some value when the
dynamical equilibrium between the tumour and the immune system is reached. In the
case of the medium antigen presentation, both these regimes can be realized depending
on the initial tumour size and the condition of the immune system. A pronounced
immunomodulating effect (the suppression of tumour growth and the normalization of
IL-2 concentration) is established by considering the influence of low-intensity
electromagnetic microwaves as a parametric perturbation of the dynamical system. This
finding is in qualitative agreement with the recent experimental results on
immunocorrective effects of centimetre electromagnetic waves in tumour-bearing mice.
Keywords: carcinogenesis; interleukin-2; modelling; anti-tumour immunity;
electromagnetic waves
2024-09-02 | BIOMD0000000910 | BioModels