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Series GSE138698 Query DataSets for GSE138698
Status Public on Jul 06, 2021
Title An engineered IL-2 partial agonist promotes CD8+ T cell stemness
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients . Both the number of transferred T cells and their differentiation state are critical determinants of effective responses. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells and lower therapeutic efficacy, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that were expanded with H9T showed robust anti-tumour activity in vivo in models of melanoma and acute lymphoblastic leukaemia. Thus, using engineered cytokine variants with distinctive properties is a promising strategy, with broad translational potential.
Overall design ChIP-Seq, RNA-Seq and ATAC-Seq analyses using TCR pre-activated CD8+ T cells that were expanded with either no cytokine, or with IL-2, H9 or H9T.
Contributor(s) Mo F, Yu Z, Li P, Oh J, Spolski R, Zhao L, Glassman CR, Yamamoto TN, Chen Y, Golebiowski FM, Hermans D, Majri SS, Picton L, Liao W, Ren M, Zhuang X, Mitra S, Lin J, Gattinoni L, Powell JD, Restifo NP, Garica K, Leonard WJ
Citation(s) 34526724
Submission date Oct 10, 2019
Last update date Oct 01, 2021
Contact name Peng Li
Organization name NIH
Department NHLBI
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (2)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (71)
GSM4116400 RNA-Seq preA d0 rep1
GSM4116401 RNA-Seq preA IL-2 d2 rep1
GSM4116402 RNA-Seq preA H9 d2 rep1
BioProject PRJNA576860
SRA SRP225069

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Supplementary file Size Download File type/resource
GSE138698_RAW.tar 5.1 Gb (http)(custom) TAR (of BED, RPKM)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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