EV_DNA_integration
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB83979 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Antigen processing and presentation (APP) is essential for adaptive immunosurveillance in all nucleated cells. Here we describe a novel mechanism through which secreted factors other than cytokines, specifically extracellular vesicles (EVs) released from activated T cells (ATEVs) drive a positive feedback loop that enhances antigen presentation and immune responses in normal physiology and cancer. ATEV-induced immunogenicity relies on extravesicular double-stranded DNA (EVDNA) and granzyme B (Gzmb). ATEV-DNA is notably abundant, primarily consisting of genomic DNA enriched in copies of specific genes, including numerous APP machinery genes. Mechanistically, ATEV transfer of APP machinery genes to recipient dendritic or tumor cells is facilitated by Gzmb disruption of recipient cell nuclear integrity. DNAse treatment of ATEVs removed the majority of EVDNA, preventing APP machinery upregulation in recipient cells, which in turn failed to recruit T lymphocytes into tumors. Notably, ATEVs hold promise as an immune-boosting therapeutic, particularly in restoring MHC-I antigen processing and presentation, and synergize with checkpoint blockade therapy in several immunotherapy-refractory tumors. Collectively, our findings uncover a novel mechanism through which ATEVs boost APP and anti-tumor immunity. Gzmb-mediated nuclear transfer opens new avenues for non-viral gene delivery, offering potential for enhanced intranuclear gene transport and expression efficiency.
2025-03-06 | GSE290972 | GEO
Project description:Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Histone methylation was involved in anti-tumor immunity of ICB. However, the link between histone methylation and MHC-I regulation and the related mechanisms are poorly understood. Here we show that KDM5A, an H3K4 demethylase that is critical for MHC-I expression and associated antigen presentation capacity, induces robust immune response and enhances ICB efficacy. Mechanistically, KDM5A upregulates IFN-gamma/STAT1-mediated MHC-I expression via directly binding and suppressing Scos1 in tumor cells. The genes encoding the lysosomal cathepsins are recognized and up-regulated by KDM5A, resulting in enhanced antigen-presentation abilities of both tumor cells and dendritic cells. Furthermore, pharmacological enhancing KDM5A improves response to anti-PD-1 therapy. These investigations demonstrate that enhancing KDM5A triggers MHC-associated antigen presentation of both tumor cells and DCs simultaneously to boost antitumor immunity, thus represents a candidate ICB sensitizer.
2024-03-31 | GSE260912 | GEO
Project description:Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Histone methylation was involved in anti-tumor immunity of ICB. However, the link between histone methylation and MHC-I regulation and the related mechanisms are poorly understood. Here we show that KDM5A, an H3K4 demethylase that is critical for MHC-I expression and associated antigen presentation capacity, induces robust immune response and enhances ICB efficacy. Mechanistically, KDM5A upregulates IFN-gamma/STAT1-mediated MHC-I expression via directly binding and suppressing Scos1 in tumor cells. The genes encoding the lysosomal cathepsins are recognized and up-regulated by KDM5A, resulting in enhanced antigen-presentation abilities of both tumor cells and dendritic cells. Furthermore, pharmacological enhancing KDM5A improves response to anti-PD-1 therapy. These investigations demonstrate that enhancing KDM5A triggers MHC-associated antigen presentation of both tumor cells and DCs simultaneously to boost antitumor immunity, thus represents a candidate ICB sensitizer.
2025-08-30 | GSE256056 | GEO
Project description:Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Histone methylation was involved in anti-tumor immunity of ICB. However, the link between histone methylation and MHC-I regulation and the related mechanisms are poorly understood. Here we show that KDM5A, an H3K4 demethylase that is critical for MHC-I expression and associated antigen presentation capacity, induces robust immune response and enhances ICB efficacy. Mechanistically, KDM5A upregulates IFN-gamma/STAT1-mediated MHC-I expression via directly binding and suppressing Scos1 in tumor cells. The genes encoding the lysosomal cathepsins are recognized and up-regulated by KDM5A, resulting in enhanced antigen-presentation abilities of both tumor cells and dendritic cells. Furthermore, pharmacological enhancing KDM5A improves response to anti-PD-1 therapy. These investigations demonstrate that enhancing KDM5A triggers MHC-associated antigen presentation of both tumor cells and DCs simultaneously to boost antitumor immunity, thus represents a candidate ICB sensitizer.
2025-08-30 | GSE256048 | GEO
Project description:Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity
| PRJNA1222873 | ENA
Project description:Tumor mutational burden (TMB), usually representing high immunogenicity, could not always predict treatment response of immune checkpoint blockade (ICB). Here, we showed that defective antigen cross-presentation in type 1 conventional dendritic cells (cDC1) was responsible for lacking tumor-specific cytotoxic T lymphocytes (CTLs) in triple-negative breast cancer (TNBC) patients. Mechanistically, tumor cytosolic CDC37, shuttled via extracellular vesicles (EVs) into the endosomes of intratumor DCs, inhibited antigen cross-presentation by locking antigen binding to HSP90 and precluding their translocation from endosomes to cytoplasm. CDC37 knockdown in tumor cells or inhibiting CDC37/HSP90 interaction in DCs efficiently promoted antigen translocation and enhanced their cross-presentation, which improved ICB therapeutic responses. Clinically, high tumor CDC37 expression was associated with low infiltration of antigen-specific CTLs and poor ICB efficacy in TNBC patients. Therefore, tumor EV-shuttled CDC37 locks antigen/chaperone interaction and impairs antigen cross-presentation in DCs. Moreover, targeting CDC37 is promising to enhance anti-tumor immunity and reverse ICB resistance.
2025-10-17 | PXD069576 |
Project description:Targeting cathepsin B by cycloastragenol enhances anti-tumor immunity via inhibiting MHC-1 degradation and promoting the presentation of tumor antigen
| PRJNA809393 | ENA
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