Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1055507 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Universal STING Mimic Boosts Antitumour Immunity via Preferential Activation of Tumour Control Signalling Pathways
| PRJNA1066759 | ENA
Project description:Universal STING Mimic Boosts Antitumour Immunity via Preferential Activation of Tumour Control Signalling Pathways
| PRJNA1066825 | ENA
Project description:The efficacy of stimulator of interferon genes (STING) agonists is compromised by various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours and a complex balance between tumour control and progression. Here, we report a universal STING mimic (uniSTING) based on a polymeric architecture. The uniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNP) results in potent anti-tumour efficacy across established and advanced metastatic tumour models, including triple negative breast cancer, lung cancer, melanoma and orthotopic/metastatic liver malignancies. Furthermore, uniSTING displays an effective antitumour response superior to 2’3’-cGAMP and ADU-S100. By favouring IRF3/IFN-I activity over the pro-inflammatory NF-κB signalling pathway, uniSTING promotes dendritic cell maturation and antigen specific CD8+ T cell responses. Extracellular vesicles released from uniSTING-treated tumour cells further sensitise dendritic cells via exosome containing miRNAs that reduced the immunosuppressive Wnt2b and a combination of LNP-uniSTING-mRNA with α-Wnt2b antibodies synergistically inhibit tumour growth and prolong animal survival. Collectively, these results demonstrate the LNP-mediated delivery of uniSTING-mRNA as a strategy to overcome the current STING therapeutic barriers, particularly for the treatment of multiple cancer types in which STING is downregulated or absent.
2024-01-22 | GSE253724 | GEO
Project description:The efficacy of stimulator of interferon genes (STING) agonists is compromised by various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours and a complex balance between tumour control and progression. Here, we report a universal STING mimic (uniSTING) based on a polymeric architecture. The uniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNP) results in potent anti-tumour efficacy across established and advanced metastatic tumour models, including triple negative breast cancer, lung cancer, melanoma and orthotopic/metastatic liver malignancies. Furthermore, uniSTING displays an effective antitumour response superior to 2’3’-cGAMP and ADU-S100. By favouring IRF3/IFN-I activity over the pro-inflammatory NF-κB signalling pathway, uniSTING promotes dendritic cell maturation and antigen specific CD8+ T cell responses. Extracellular vesicles released from uniSTING-treated tumour cells further sensitise dendritic cells via exosome containing miRNAs that reduced the immunosuppressive Wnt2b and a combination of LNP-uniSTING-mRNA with α-Wnt2b antibodies synergistically inhibit tumour growth and prolong animal survival. Collectively, these results demonstrate the LNP-mediated delivery of uniSTING-mRNA as a strategy to overcome the current STING therapeutic barriers, particularly for the treatment of multiple cancer types in which STING is downregulated or absent.
2024-01-24 | GSE253681 | GEO
Project description:Lytic cell death triggers an antitumour immune response. However, cancer cells evade lytic cell death by several mechanisms. Moreover, a prolonged uncontrolled immune response conversely leads to T-cell exhaustion. Therefore, an oncolytic system capable of eliciting the immune response by dissolving cancer cells in a controlled manner is needed. Here, we establish a micro-scale cytotoxic T-cell-inspired oncolytic system (TIOs) to precisely lyse cancer cells by NIR-light-controlled lipid peroxidation. Our TIOs present antigen-based cell recognition, tumour-targeting and catalytic cell-lysis ability; thus, the TIOs induce oncolysis in vivo. We applied TIOs to antitumour therapies, which shows kinds of tumour models are cleared efficiently with negligible side-effects. Tumour regression is correlated with a T-cell based anti-tumour immune response and can be synergistic with anti-PD-1 therapy or STING activation. Our study provides new insights to design the oncolytic systems for antitumour immunity. Moreover, activation of STING can reverse T-cell exhaustion in oncolysis.
2023-09-05 | PXD044912 | Pride
Project description:Lytic cell death, such as pyroptosis, can trigger antitumour immune response. However, cancerous cells avoid lytic cell death by various escape mechanisms acquired through evolution. Moreover, persistent uncontrolled lytic cell death may inversely cause hyperactive immune response or T-cell exhaustion. Therefore, an oncolytic system capable of breaking through natural restrictions to dissolve cancer cells in a catalytic and controllable manner is needed. Here, we established a microscale cytotoxic T-cell-inspired oncolytic system (TIOs) by which the NIR light-generated reactive oxygen species could precisely rupture the plasma membrane of cancer cells by direct lipids peroxidation. Similar as cytotoxic T cells, TIOs present antigen-based cell recognition and catalytic cell-lysis ability; thus, the TIOs can trigger significant oncolysis and immune response in vivo. The TIOs exhibited exceptional tumour targeting and penetration without any inflammatory risk. We applied TIOs to antitumour therapies, which showed kinds of tumour models could be cleared efficiently with negligible injuries to major organs. Tumour regression was correlated with oncolysis-mediated inflammation and T-cell-based antitumor immune response. Owing to the tuneability of TIOs-mediated oncolysis, we further revealed that though the T-cell recruitment was comparable, the high-intense oncolysis induced acute inflammation in initial stage was crucial for potent antitumour immunity and immune memory effects, and low-intense oncolysis resulted in T-cell exhaustion and tumour progression. To the mice received low-intense oncolysis, although synergizing with anti-PD-1 therapies or STING activation rescued the immune dysfunction, STING activation released a more powerful boost to durative antitumour immunity by reshaping the stemness of CD8+ T cells. Our study provides new insights to design the oncolytic systems for antitumour immunity. Moreover, our application suggests that the intensity of initial inflammation plays a decisive role in maintaining oncolysis-induced antitumour immune function and STING activation holds promise for reversal of immune dysfunction due to T-cell exhaustion.
2023-08-22 | GSE227675 | GEO
Project description:STING signalling compensates for low tumour mutation burden to drive anti-tumour immunity
| PRJNA1073532 | ENA
Project description:Current chemotherapy or immunotherapy regimens for pancreatic cancer are limited. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for unresectable pancreatic cancers, the typical immunosuppressive tumour microenvironment promotes immune evasion and rapid tumour recurrence. Thus, triggering efficient amplification of endogenous adaptive antitumour immunity is critical for improving immunotherapy after ablation therapy. Here, we developed a hydrogel microsphere vaccine as an immune amplifier for post-ablation cancer immunotherapy. The vaccine acts as a general immune amplifier to trigger a rocket-like amplification of the cDC1-mediated antigen cross-presentation cascade, resulting in dramatic amplification of the antitumour immunity of endogenous CD8+ T cells. We also showed that the hydrogel microsphere vaccine promoted the transformation of pancreatic cancer from "cold" to "hot" tumours in a safe and efficient manner, significantly increased the survival of mice bearing orthotopic pancreatic tumours, and induced strong systemic antitumour immunity, which inhibited the growth of distant metastases.
2023-05-22 | GSE215417 | GEO
Project description:Survival of malignant tumours is highly relevant to their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy, yet precisely dismantling self-defenses to amplify antitumour potency remains unexplored. Herein, we demonstrate that nanoparticles-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade selectively modulates heat shock factor 1 to suppress dual self-defense pathways for potentiating thermo-immunotherapy. TRPV1 blockade is identified to inhibit calcium influx and subsequent nuclear translocation of HSF1 upon hyperthermia, leading to selective suppression of stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumours. Particularly, the suppression of HSF1 translocation further restrains TGFβ pathway to apparently degrade extracellular matrix in tumour for improving the infiltration of antitumour therapeutics and immune cells into highly fibrotic and immunosuppressive pancreatic cancers, ultimately synergizing with anti-PD-L1 antibody to retrieve thermo-immunotherapy with tumour-eradicable and immune memory effects. The nanoparticles-mediated TRPV1 blockade represents as an effective and universal approach to selectively dismantle self-defenses for potent cancer therapy.
2022-03-24 | GSE199299 | GEO
Project description:Understanding MoA of ceralasertib (AZD6738) in driving efficacy through immune regulation via T-cells and tumour intrinsic pathways (STING/IFN) for AZD6738 driven efficacy.
2024-01-29 | E-MTAB-13703 | biostudies-arrayexpress