Summary of Study ST001838

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001160. The data can be accessed directly via it's Project DOI: 10.21228/M8RT34 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001838
Study TitleReversing Epigenetic Gene Silencing to Overcome Immune Evasion in CNS Malignancies
Study SummaryGlioblastoma is an aggressive brain malignancy with a dismal prognosis. With emerging evidence that disproves the immune privileged environment in the brain, there is much interest in examining various immunotherapy strategies to treat these incurable cancers. Unfortunately, to date, clinical studies investigating immunotherapy regimens have not provided much evidence of efficacy, leading to questions about the suitability of immunotherapy strategies for these tumors. Inadequate inherent populations of lymphocytes in tumor (TILs) and limited trafficking of systemic circulating T cells into the central nervous system (CNS) likely contribute to the poor response to immunotherapy treatment for primary CNS cancers. This paucity of TILs is in concert with the finding of epigenetic silencing of genes that promote immune cell movement (chemotaxis) to the tumor. In this study we evaluated the ability of GSK126, a blood-brain barrier permeable small molecule inhibitor of EZH2, to reverse the epigenetic silencing of chemokines like CXCL9 and CXCL10. When combined with anti-PD-1 treatment, these IFN driven chemokines promote T cell infiltration, resulting in decreased tumor growth and enhanced survival in immunocompetent murine sub-cutaneous and intracranial tumor syngeneic models of GBM. Examination of the tumor micro-environment revealed that the decrease in tumor growth in the mice treated with the drug combination was accompanied by increased tumor CD8 T cell infiltration along with higher IFN expression. Additionally, a significant increase in CXCR3+ T cells in the draining lymph nodes was also found. Taken together, our data suggests that in glioblastoma, epigenetic modulation using GSK126 could improve current immunotherapy strategies by reversing the epigenetic changes that enable immune cell evasion leading to enhanced immune cell trafficking to the tumor.
Institute
National Cancer Institute
DepartmentNeuro-Oncology Branch
LaboratoryCancer Metabolism
Last NameDowdy
First NameTyrone
Address37 convent dr, Bldg 37 rm 1142
Emailtyrone.dowdy@nih.gov
Phone2407607066
Submit Date2021-06-11
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2021-06-30
Release Version1
Tyrone Dowdy Tyrone Dowdy
https://dx.doi.org/10.21228/M8RT34
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Gsk Exposure Time (h)
SA171094blank_S22.dblank -
SA171095Blank_S14.dblank -
SA171096blank_Sr62.dblank -
SA170972SubCu7_Tum_g1_10GSK 10
SA170973SubCu7_DLN_g1_10GSK 10
SA170974SubCu7_NLN_g1_10GSK 10
SA170975SubCu8_NLN_g1_10GSK 10
SA170976SubCu8_DLN_g1_10GSK 10
SA170977SubCu8_Tum_g1_10GSK 10
SA170978LLN_g1 _Intra8_10hGSK 10.0
SA170979LLN_g1 _Intra7_10hGSK 10.0
SA170980SER_g1 _Intra8_10hGSK 10.0
SA170981SER_g1 _Intra7_10hGSK 10.0
SA170982SER_g1 _Subcutaneous8_10hGSK 10.0
SA170983SER_g1 _Subcutaneous7_10hGSK 10.0
SA170984BRN_g1 _Intra8_10hGSK 10.0
SA170985BRN_g1 _Intra7_10hGSK 10.0
SA170986SER_g1 _Subcutaneous3_2hGSK 2.0
SA170987SER_g1 _Subcutaneous2_2hGSK 2.0
SA170988SER_g1 _Subcutaneous1_2hGSK 2.0
SA170989SER_g1 _Intra3_2hGSK 2.0
SA170990LLN_g1 _Intra1_2hGSK 2.0
SA170991LLN_g1 _Intra3_2hGSK 2.0
SA170992SER_g1 _Intra1_2hGSK 2.0
SA170993SER_g1 _Intra2_2hGSK 2.0
SA170994LLN_g1 _Intra2_2hGSK 2.0
SA170995BRN_g1 _Intra2_2hGSK 2.0
SA170996BRN_g1 _Intra3_2hGSK 2.0
SA170997BRN_g1 _Intra1_2hGSK 2.0
SA170998SubCu1_Tum_g1_2hGSK 2.00
SA170999SubCu1_NLN_g1_2hGSK 2.00
SA171000SubCu3_Tum_g1_2hGSK 2.00
SA171001SubCu2_NLN_g1_2hGSK 2.00
SA171002SubCu2_Tum_g1_2hGSK 2.00
SA171003SubCu2_DLN_g1_2hGSK 2.00
SA171004SubCu3_NLN_g1_2hGSK 2.00
SA171005SubCu1_DLN_g1_2hGSK 2.00
SA171006SubCu3_DLN_g1_2hGSK 2.00
SA171007SER_g1 _Subcutaneous5_6hGSK 6.0
SA171008BRN_g1 _Intra4_6hGSK 6.0
SA171009SER_g1 _Subcutaneous4_6hGSK 6.0
SA171010SER_g1 _Subcutaneous6_6hGSK 6.0
SA171011BRN_g1 _Intra5_6hGSK 6.0
SA171012LLN_g1 _Intra4_6hGSK 6.0
SA171013LLN_g1 _Intra6_6hGSK 6.0
SA171014SER_g1 _Intra5_6hGSK 6.0
SA171015SER_g1 _Intra4_6hGSK 6.0
SA171016SER_g1 _Intra6_6hGSK 6.0
SA171017SubCu6_NLN_g1_6hGSK 6.00
SA171018SubCu6_Tum_g1_6hGSK 6.00
SA171019SubCu5_NLN_g1_6hGSK 6.00
SA171020SubCu4_DLN_g1_6hGSK 6.00
SA171021SubCu5_DLN_g1_6hGSK 6.00
SA171022SubCu4_NLN_g1_6hGSK 6.00
SA171023SubCu4_Tum_g1_6hGSK 6.00
SA171024SubCu5_Tum_g1_6hGSK 6.00
SA171025SubCu6_DLN_g1_6hGSK 6.00
SA171026QCpool g1 D_NLN_subcu_028.dQC -
SA171027QCpool g1 D_NLN_subcu_037.dQC -
SA171028QCpool g1 D_NLN_subcu_081.dQC -
SA171029QCpool g1 D_NLN_subcu_012.dQC -
SA171030QCpool g1 SubTum_038.dQC -
SA171031QCpool g1 D_NLN_subcu_135.dQC -
SA171032QCpool g1 SubTum_136.dQC -
SA171033QCpool g1 D_NLN_subcu_055.dQC -
SA171034QcSer_S44.dQC -
SA171035QcSer_S24.dQC -
SA171036QCpool g1 SubTum_082.dQC -
SA171037QCpool g1 SubTum_056.dQC -
SA171038QcBRN_S45.dQC -
SA171039QcLLN_L1002.dQC -
SA171040QcBRN_Sr111.dQC -
SA171041QcBRN_Sr91.dQC -
SA171042QcBRN_Sr65.dQC -
SA171043SER_ctrl_g2_Intra11_2hVehicle 0.0
SA171044SER_ctrl_g2_Intra12_6hVehicle 0.0
SA171045SER_ctrl_g2_Intra13_6hVehicle 0.0
SA171046SER_ctrl_g2_Intra10_2hVehicle 0.0
SA171047SER_ctrl_g2_Subcutaneous14_6hVehicle 0.0
SA171048SER_ctrl_g2_Subcutaneous13_6hVehicle 0.0
SA171049SER_ctrl_g2_Intra14_6hVehicle 0.0
SA171050SER_ctrl_g2_Subcutaneous15_10hVehicle 0.0
SA171051SER_ctrl_g2_Subcutaneous16_10hVehicle 0.0
SA171052SER_ctrl_g2 _Intra9_2hVehicle 0.0
SA171053BRN_ctrl_g2_Intra13_6hVehicle 0.0
SA171054BRN_ctrl_g2_Intra12_6hVehicle 0.0
SA171055BRN_ctrl_g2_Intra11_2hVehicle 0.0
SA171056BRN_ctrl_g2_Intra10_2hVehicle 0.0
SA171057BRN_ctrl_g2_Intra14_6hVehicle 0.0
SA171058BRN_ctrl_g2_Intra15_10hVehicle 0.0
SA171059SER_ctrl_g2_Intra16_10hVehicle 0.0
SA171060SER_ctrl_g2_Subcutaneous10_2hVehicle 0.0
SA171061BRN_ctrl_g2_Intra16_10hVehicle 0.0
SA171062SER_ctrl_g2_Intra15_10hVehicle 0.0
SA171063SER_ctrl_g2_Subcutaneous12_6hVehicle 0.0
SA171064LLN_ctrl_g2_Intra13_6hVehicle 0.0
SA171065LLN_ctrl_g2_Intra12_6hVehicle 0.0
SA171066LLN_ctrl_g2_Intra15_10hVehicle 0.0
SA171067LLN_ctrl_g2_Intra16_10hVehicle 0.0
SA171068LLN_ctrl_g2 _Intra9_2hVehicle 0.0
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