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Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas

UID: 10632

Author(s): Amoozgar, Zohreh, Kloepper, Jonas, Ren, Jun, Tay, Rong E., Kazer, Samuel W., Kiner, Evgeny, Krishnan, Shanmugarajan, Posada, Jessica M., Ghosh, Mitrajit, Mamessier, Emilie, Wong, Christina, Ferraro, Gino B., Batista, Ana, Wang, Nancy, Badeaux, Mark, Roberge, Sylvie, Xu, Lei, Huang, Peigen, Shalek, Alex K., Fukumura, Dai, Kim, Hye-Jung, Jain, Rakesh K.

Description
Summary from the GEO: "Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma (GBM) trials. Here, we show that regulatory T (Treg) cells play a key role in GBM resistance to ICBs in experimental gliomas. Targeting glucocorticoid-induced TNFR-related receptor (GITR) in Treg cells using an agonistic antibody (αGITR) promotes CD4 Treg cell differentiation into CD4 effector T cells, alleviates Treg cell-mediated suppression of anti-tumor immune response, and induces potent anti-tumor effector cells in GBM. The reprogrammed GBM-infiltrating Treg cells express genes associated with a Th1 response signature, produce IFNγ, and acquire cytotoxic activity against GBM tumor cells while losing their suppressive function. αGITR and αPD1 antibodies increase survival benefit in three experimental GBM models, with a fraction of cohorts exhibiting complete tumor eradication and immune memory upon tumor re-challenge. Moreover, αGITR and αPD1 synergize with the standard of care treatment for newly-diagnosed GBM, enhancing the cure rates in these GBM models."

Overall Design from the GEO: "Treg cells were sorted from IgG (control; spleen n=7; tumor n=5) or aGITR+aPD1 (treated; spleen n=9; tumor=7) treated GBM-bearing mice. Each individual spleen or tumor sample was harvested from different mice, respectively."
Subject of Study
Mus musculus
Subject(s)
Glioblastoma
Immune Checkpoint Inhibitors
T-Lymphocytes, Regulatory
OncoTree Cancer Type(s)
Glioblastoma
Glioblastoma Multiforme
Access via GEO

Plain Text Data of expression profiling by high throughput sequencing
Accession #: GSE167746

Access via SRA

RNA Sequence reads for 28 samples
Accession #: SRP308387

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA705184

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Amoozgar Z, Kloepper J, Ren J, et al. Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas. Nat Commun. 2021;12(1):2582. Published 2021 May 11.
Data Type
Genomic
Equipment Used
Illumina NextSeq 500
Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
Plain Text, gzip
Data Tool(s)
RNA Seq
Dataset Size
1.6 MB
Data Catalog Record Updated
2023-12-07