Gene expression data from CD11b-positive myeloid cells infiltrating tumors after local irradiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE45180 | GEO | 2013/12/31
SECONDARY ACCESSION(S): PRJNA193154
REPOSITORIES: GEO
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Project description:Analysis of global gene expression in myeloid cells infiltrating tumors after irradiation. Cell death induces recruitment of myeloid cells into irradiated tumors thereby stimulating tumor recurrence. Results provide insights into molecular mechanisms regulating tumorigenic functions of myeloid cells in tumors re-growing after radiation therapy. Samples were collected at day 4 from irradiated tumors in WT, TLR9KO and Stat3KO (MxCre/Stat3flox). There were total 11 samples with 3-4 replicates of each sample type.
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Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
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Project description:This study uses microarray analysis to examine the fate of multiple C-ion-irradiated tumors in vivo to gain a comprehensive overview of the changes in gene expression induced by C-ion irradiation. Four murine tumors were irradiated in vivo with C-ions at a single dose, and gamma-rays were used as a reference beam. Keywords: mouse squamous cell carcinoma and fibrosarcoma, carbon ion-irradiation, gamma-irradiation, resected sample, transplanted tissues
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Project description:Radiotherapy can act as in situ vaccine activating preventive tumor-specific immune responses in treated patients. While carbon ion radiotherapy holds superior biophysical properties over conventional photon irradiation, little is known about the immunological effects induced by this radiation type. Multiple strategies combining radiotherapy with immune checkpoint inhibition (radioimmunotherapy) to enhance anti-tumor immunity have been described, however, results on the immune cell composition in tumors following radioimmunotherapy with carbon ions are lacking. Here, we present a bilateral tumor model based on time-shifted transplantation of murine, Her2+ EO771 tumor cells onto the flanks of immune competent mice followed by selective irradiation of the primal tumor. αCTLA4- but not αPD-L1-based radioimmunotherapy induced complete tumor rejection and mediated eradication of even non-irradiated, distant tumors. Cured mice were protected against EO771 rechallenge indicative of long lasting, tumor-specific immunological memory. Single cell RNA-sequencing and flow cytometric analyses of irradiated tumors revealed activation of NK cells and distinct tumor-associated macrophage clusters with upregulated expression of TNF and IL1 responsive genes. Distant tumors of irradiated mice showed higher frequencies of naïve T cells, which were activated upon combination with CTLA4 blockade. Thus, radioimmunotherapy with carbon ions plus CTLA4 inhibition reshapes the tumor-infiltrating immune cell composition and can induce complete rejection even of non-irradiated tumors. Our data suggest to combine radiotherapy approaches with CTLA4 blockade to achieve durable anti-tumor immunity. Furthermore, evaluation of future radioimmunotherapy approaches should not be restricted to immunological impacts at the irradiation site, but should also consider systemic immunological effects on non-irradiated tumors.
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Project description:NK-92 cells and their CAR-modified derivatives exhibit strong cytotoxic activity against tumors and are promising "off-the-shelf" therapeutics compared to CAR-T cells. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cells need to be inactivated before transfusion. With increasing clinical use, there is a growing demand for enhanced safety and an efficient method that stops cell proliferation, but better maintains the cytotoxic effector functions of the cells compared to commonly used gamma irradiation. Recently, low-energy electron irradiation (LEEI) was successfully applied for inactivation of bacteria and viruses for vaccine production, and was described as a method for NK-92 inactivation for the first time. In the present publication, data on extensive characterization of LEEI and its comparison with gamma irradiation for the inactivation of parental NK-92 cells as well as CD123-directed CAR-NK-92 cells are provided. Our results show that both irradiation methods cause a progressive decrease in cell viability and are therefore suitable for inhibition of proliferation. Notably, cytotoxicity of the NK cells was significantly reduced by gamma irradiation, but not by LEEI three days after irradiation, compared to non-irradiated cells. Both gamma irradiation as well as LEEI led to substantial DNA-damage and an accumulation of irradiated cells in the G2/M phase. In addition, transcriptomic analysis of cells irradiated with both methods revealed approximately 12-fold more differentially expressed genes after gamma irradiation compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in CD56 expression but no changes in the levels of the activating receptors NKp46, NKG2D, and NKp30. Conclusions: The present data show that LEEI efficiently inactivates (CAR )NK-92 cells and sustains their cytotoxic capacity better than gamma irradiation. Taking into account additional logistic advantages of LEEI proves a potent alternative in the manufacturing of (CAR-)NK-92 cells for clinical application.
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Project description:Question Addresses: What is the gene expression profile from human umbilical vein endothelial cells (HUVEC) and human Jurkat T cells after irradiation (IR)? What, if any, is the effect of co-culturing these two cell types on gene expression? There are eight experimental conditions for this experiment: (1) non-irradiated HUVEC; (2) irradiated HUVEC; (3) non-irradiated Jurkat; (4) irradiated Jurkat; (5) non-irradiated HUVEC + non-irradiated Jurkat+; (6) non-irradiated HUVEC + irradiated Jurkat; (7) irradiated HUVEC + non-irradiated Jurkat; (8) irradiated HUVEC + irradiated Jurkat. A common, pooled reference consisting of RNA taken from conditions 1-8 as described above was used for all hybridizations.
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Project description:The aim of this study was to identify the transcriptomic response 6 hours after the MRT irradiation, in normal brain tissue (11 samples) and in glioma tissue (11 samples), in rat. The orthotopic tumor-bearing rats were either treated with MRT radiation (six MRT-tumors), or untreated (five No irradiated tumors). The contralateral half hemisphere without tumor received the MRT treatment for six rats (6 MRT-Contralateral samples) and no irradiation for five rats (5 Untreated contralateral samples). Six hours after treatment, the tumors and their controlateral regions were resected and analysed for transcriptomic response.
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