Effects of the treatment with IFNβ and GM-CSF-secreting CT2A cells to wildtype CT2A tumor microenvironment post resection
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PROVIDER: PRJNA898299 | ENA |
REPOSITORIES: ENA
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Project description:To elucidate the underlying immune responses elicited by IFNβ and GM-CSF-secreting CT2A cells to brain tumor microenvironment post resection compared to placebo group and non-IFNβ and GM-CSF-secreting CT2A cell group
2022-11-09 | GSE217253 | GEO
Project description:Molecular profiling of SV-BR-1-GM, a clinically effective GM-CSF-secreting human breast cancer cell line
| PRJNA445326 | ENA
Project description:A common cornerstone of preclinical cancer research is the use of syngeneic orthotopic murine tumors as immunocompetent models of human cancers. For glioblastoma research efforts, the GL261 and CT2A lines are frequently used. We systematically characterized these two lines to decipher the cell-intrinsic mechanisms that drive immuno-resistance in CT2A and to define the aspects of human cancer biology that the lines best model. We show that, despite sharing a few canonical genetic or histologic features of human glioblastoma, the transcriptional profiles of GL261 and CT2A tumours most closely resembled those of glioblastomas. CT2A additionally resembled other cancer types transcriptionally, including melanoma. CT2A displayed mesenchymal differentiation, upregulated angiogenesis, and multiple defects in antigen presentation machinery and interferon response pathways. Loss of MHC class I expression was restored in CT2A by interferon-γ treatment, explaining in part the modest efficacy of some immunotherapy combinations for CT2A. Our findings indicate that CT2A may serve as a robust preclinical solid tumor model of adaptive immune resistance.
2023-12-19 | PXD036720 | Pride
Project description:The SV-BR-1 cell line was derived from a chest wall lesion of a breast cancer patient. SV-BR-1 cells were stably transfected with CSF2 (encoding GM-CSF), resulting in the SV-BR-1-GM cell line. Following irradiation to prevent cell replication, both SV-BR-1 (Wiseman and Kharazi, The Open Breast Cancer Journal, 2010, 2, 4-11) and SV-BR-1-GM (Wiseman and Kharazi, Breast J. 2006 Sep-Oct;12(5):475-80) cells have been applied as whole-cell therapeutics in clinical trial settings for advanced breast cancer. Molecular profiles of non-irradiated SV-BR-1-GM cells have been established from various manufacturing lots via Illumina HumanHT-12 V4.0 expression beadchip arrays (GPL10558). A key finding from the study is the identification of an immune signature expressed in SV-BR-1-GM cells which includes the MHC class II factors HLA-DMA, HLA-DMB, HLA-DRA, and HLA-DRB3. Since tumor regressions were apparent in clinical trial subjects matching at an HLA-DRB3 allele with SV-BR-1-GM we hypothesize that (partial) HLA matching is needed for maximal tumor-directed clinical responses to occur.
2018-03-23 | GSE112239 | GEO
Project description:BACKGROUND: While many authorities theorize that cancer vaccines are too weak to be widely effective, there are quite a few reports with clearly demonstrated, significant clinical benefit in some patients. The literature of cellular cancer immunotherapies shows that 53% (78/147) of phase II studies showed evidence of clinical activity. While not all reached their primary endpoints, 75% (12/16) of phase III studies had positive data. SV-BR-1-GM, derived from a patient with grade 2 (moderately differentiated) breast cancer, is a GM-CSF-secreting breast cancer cell line with properties of antigen-presenting cells we established. METHODS: We report detailed molecular and clinical findings from an open-label phase I, single-arm pilot study in breast (3 subjects) and ovarian (1 subject) cancer with irradiated SV-BR-1-GM cells (ClinicalTrials.gov Identifier NCT00095862). Inoculations of SV-BR-1-GM were preceded by low-dose cyclophosphamide and followed by injections of interferon-alpha2b into the SV-BR-1-GM inoculation sites. We assessed both cellular (delayed-type hypersensitivity (DTH) reactions) and humoral (anti-SV-BR-1 antibody) immune responses and conducted molecular analyses on patient blood cells and SV-BR-1-GM cells. RESULTS: Treatment was generally safe and well tolerated. Immune responses were elicited universally. Overall survival was more than 33 months for three of the four patients. As previously reported, one patient (Subject A002, with grade 2 breast cancer) had regression of metastases in lung, breast and soft tissue within 2 months of treatment initiation. At later relapse, with multiple metastases including several in the brain, rapid tumor response was again seen, including complete regression of CNS metastases. Consistent with a role of Class II HLA in contributing to SV-BR-1-GM’s mechanism of action, Subject A002 allele-matched SV-BR-1-GM at the HLA-DRB1 and HLA-DRB3 loci. Only the HLA-DRB1 alleles were clearly expressed in SV-BR-1-GM cells. However, interferon-gamma (possibly also present in situ) upregulated both HLA-DRB1 and HLA-DRB3 to substantial levels. Gene expression data supports the hypothesis that SV-BR-1-GM cells have retained some of the original breast cancer’s grade 2 character. CONCLUSIONS: We describe a whole-cell immunotherapy regimen with remarkable rapidity of response and a speedy rescue response, including complete resolution of CNS metastases after relapse. Class II HLA matches might be critical for SV-BR-1-GM’s therapeutic potential.
2022-06-23 | PXD020304 | Pride
Project description:To investigate the role of LDHA in regulating gene expression in glioma cells, we treated CT2A glioma cells with LDHA inhibitor FX11. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and FX11-treated cells.
2023-11-09 | GSE216070 | GEO
Project description:Transcriptional profiling of human peripheral B cell subsets sorted by flow cytometry based on the secretion of IL-10 in response to CpG2006 stimulation. Goal was to identify molecular markers to distinguish IL-10-producing B cells form non-IL-10-producing B cells. Two-condition experiment, non-IL-10-secreting B cells vs. IL-10-secreting B cells. Healthy donors. Biological replicates: 6
2013-03-04 | E-GEOD-35002 | biostudies-arrayexpress
Project description:Furfurilactobacillus rossiae strain:DSM 15814T, GM-S1_998, GM-S2_998, GM-S3_998 Genome sequencing and assembly
| PRJNA531157 | ENA
Project description:Type I IFNs are critical in initiating protective antiviral immune responses and plasmacytoid DCs (pDCs) represent a major source of these cytokines. Here we show that only few pDCs are capable to produce IFNβ after virus infection or CpG stimulation. Utilizing IFNβ/YFP reporter mice, we identify these IFNβ-producing cells in the spleen as a CCR9+CD9- pDC subset exclusively localized within the T/B cell zones. IFNβ-producing pDCs exhibit a distinct transcriptome profile with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation. These distinctive characteristics of IFNβ-producing pDCs are independent of the type I IFN receptor mediated feedback loop. Furthermore, IFNβ-producing pDCs exhibit enhanced CCR7-dependent migratory properties in vitro and in a peritoneal inflammation model they effectively recruit T cells in vivo. We define “professional type I IFN-producing cells” as a distinct subset of pDCs specialized in coordinating cellular immune responses.
2015-05-27 | GSE68788 | GEO
Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.
2020-02-19 | PXD012794 | Pride