Single-cell transcriptomics reveals ferrimagnetic vortex nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating tumor-associated macrophages suppression
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE241188 | GEO | 2024/08/01
REPOSITORIES: GEO
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Project description:Single-cell transcriptomics reveals ferrimagnetic vortex nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating tumor-associated macrophages suppression
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Project description:Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment. We investigated the effects of exogenous R-2-HG on primary human T cells.
2016-07-27 | E-GEOD-84849 | biostudies-arrayexpress
Project description:Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.
| S-EPMC7069093 | biostudies-literature
Project description:Background Clinical practice demonstrates that anticancer drug effects may strongly vary between different patients. Individual responses to drug action are potentially responsible for adverse effects such as establishment of resistance. Consequently, the understanding of response mechanisms to drug actions is of great relevance. Proteome profiling is a powerful tool for the investigation of cellular responses to drugs. Methods Here, we have investigated the effects of curcumin, a natural remedy with known anti-cancer activities, on breast cancer cells MCF-7, ZR-75-1 and normal mammary fibroblasts as well as co-cultures thereof using proteome profiling. The mammary fibroblasts had been treated before with TGF-beta in order to induce a wound-healing signature known to be representative for the in vivo situation in breast tumors. Results While co-culture alone induced several proteins like ANXA1, S100A4 and SPARC similarly in both breast cancer cells, the majority of proteins regulated upon co-culture differed between MCF-7 and ZR-75-1. Curcumin significantly induced HMOX1 in all single cell models and co-cultures. However, otherwise the curcumin effects differed. In the MCF-7 co-culture, curcumin significantly downregulated RC3H1, a repressor of inflammatory signaling. In the ZR-75-1 co-culture, curcumin significantly downregulated PEG10, an anti-apoptotic protein, and induced RRAGA, a pro-apoptotic protein involved in TNF-alpha signaling. In this model, curcumin also induced AKR1C2, an important enzyme for progesterone metabolism. None of these specific curcumin effects were observed in single cell cultures. Conclusions The present data demonstrate that curcumin induces proteome alterations potentially accounting for its known antitumor effects in a strongly context-dependent fashion.
2018-06-04 | PXD008719 | Pride
Project description:Tumor Treating Fields (TTFields) disturbs mitosis and consequently leads to cell cycle arrest and cell death. Mild hyperthermia induces cancer cell death by apoptosis,leading to DNA damage and disturbing DNA repair. Thus, when mild hyperthermia is combined with TTFields, the anti-tumor effect could be augmented. This prompted the hypothesis for the present thesis: TTFields and mild hyperthermia as synergistic modalities in Pancreatic ductal adenocarcinoma (PDAC) treatment could probably enhance antitumor efficacy and abate individual toxic effects through distinct and overlapping mechanisms target the tumor cell. Our established PDAC cell line (Bx-GEM) was treated with TTFields and TTFields with mild hyperthermia and was examined by microarray. 500 ng mRNA was checked for quality control and the concentration was measured again. Subsequently, gene expression profiling was performed using human HuGene-2_0-st-type array from Affymetrix.
2021-03-17 | E-MTAB-10270 | biostudies-arrayexpress
Project description:In this study, biologically synthesized iron oxide nanoparticles, called magnetosomes, are made fully biocompatible by removing potentially toxic organic bacterial residues such as endotoxins at magnetosome mineral core surfaces and by coating such surface with poly-L-lysine, leading to magnetosomes-poly-L-lysine (M-PLL). M-PLL antitumor efficacy is compared with that of chemically synthesized iron oxide nanoparticles (IONPs) currently used for magnetic hyperthermia. M-PLL and IONPs are tested for the treatment of glioblastoma, a dreadful cancer, in which intratumor nanoparticle administration is clinically relevant, using a mouse allograft model of murine glioma (GL-261 cell line). A magnetic hyperthermia treatment protocol is proposed, in which 25 µg in iron of nanoparticles per mm3 of tumor are administered and exposed to 11 to 15 magnetic sessions during which an alternating magnetic field of 198 kHz and 11 to 31 mT is applied for 30 minutes to attempt reaching temperatures of 43-46 °C. M-PLL are characterized by a larger specific absorption rate (SAR of 40 W/gFe compared to 26 W/gFe for IONPs as measured during the first magnetic session), a lower strength of the applied magnetic field required for reaching a target temperature of 43-46 °C (11 to 27 mT compared with 22 to 31 mT for IONPs), a lower number of mice re-administered (4 compared to 6 for IONPs), a longer residence time within tumours (5 days compared to 1 day for IONPs), and a less scattered distribution in the tumour. M-PLL lead to higher antitumor efficacy with full tumor disappearances achieved in 50% of mice compared to 20% for IONPs. This is ascribed to better ability of M-PLL, at equal iron concentrations, to maintain tumor temperatures at 43-46°C over a longer period of times.
| S-EPMC5695153 | biostudies-literature
Project description:Autophagy is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. In this study, we investigated the anti-tumor effect of combining pulsed-wave ultrasound hyperthermia (pUH) enhanced PEGylated liposomal doxorubicin (PLD) delivery with an autophagy inhibitor chloroquine (CQ). BALB/c mice bearing subcutaneous 4T1 tumor received intravenous injection of PLD (10 mg/kg) plus 15-minute on-tumor pUH on Day 5 after tumor implantation and were then fed with CQ (50 mg/kg daily) thereafter. Prolonged suppression of tumor growth was attained with PLD + pUH + CQ treatment, whereas in PLD + pUH group tumors quickly recurred after an initial inhibition. Treatment with CQ monotherapy had no benefit compared to the control group. Immunohistochemical staining and Western blotting showed that autophagy of cancer cells was blocked for the mice receiving CQ. It indicates that PLD + pUH + CQ is a promising strategy to treat cancer for a long-term inhibition.
| S-EPMC6713759 | biostudies-literature
Project description:Identification of a novel antitumor CD4+ T cell cluster orchestrating antitumor immunity
| PRJNA714138 | ENA
Project description:Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment.
2016-07-27 | GSE84849 | GEO
Project description:Physical factors can have major influences on the proliferation and differentiation fate of hematopoietic stem cells in culture. Recently, we demonstrated that cord blood CD34+ cells undergo accelerated and increased megakaryocyte differentiation when incubated at 39°C. In this study, we investigated in detail the impacts of mild hyperthermia on the kinetics of megakaryocyte differentiation, maturation, polyploidization and cell viability. The qualitative and quantitative effects on Mk differentiation were found to be rapidly induced, and optimization of the culture length at 39°C led to greater Mk yields. Mild hyperthermia did not promote endomitosis of cord blood-derived Mk, but rather led to a small reduction in the proportion of polyploid Mk. Moreover, it had little impact on viability but induced a significant shift in the proportion of cells undergoing apoptosis at 37°C to necrosis at 39°C. Finally, our results suggest that the effects on megakaryocyte differentiation could be the consequences of aberrant expression of key megakaryocyte transcription factors induced by mild hyperthermia. Keywords: Effect of mild hyperthermia on Mk differentiation
2007-12-01 | GSE9218 | GEO