GEO series

In vitro inhibition of STAT5 signaling limits CD8⁺ T-cell exhaustion and improves outcomes in adoptive T-cell therapy models.

GSE335822 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2026/07/15 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 15 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 15 samples: 5 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

T-cell exhaustion remains a barrier to adoptive cell therapies. Although γc cytokines are widely used to expand T cells, their impact on T-cell states remains incompletely defined. Using an in vitro model of repetitive TCR stimulation, we found that high-dose IL-2 or IL-15 promoted exhausted CD8⁺ T-cell (TEX) differentiation, marked by increased inhibitory receptor expression and loss of stem-like features.

Read the full summary ↓

During chronic LCMV Clone 13 infection, virus-specific CD8⁺ T cells expressing high IL2Rβ displayed features of terminally exhausted TEX cells, whereas IL2Rβ deficiency favored progenitor-like populations. In TEX cells, IL-2 and IL-15 preferentially induced STAT5 phosphorylation relative to other signaling pathways. Genetic disruption of STAT5 similarly supported progenitor subsets, implicating STAT5 in the progression toward more differentiated TEX states under chronic stimulation. We therefore asked whether transient attenuation of STAT5 signaling during in vitro T-cell expansion could bias differentiation toward progenitor-like populations without compromising functional competence. Transient JAK3 or STAT5 inhibition enriched for TCF1⁺Ly108⁺ progenitor-like cells while preserving cytokine production and degranulation capacity. Following transfer into tumor-bearing mice, cells expanded under STAT5-inhibited (STAT5i) conditions mediated superior tumor control and prolonged survival. Likewise, transient STAT5 inhibition preserved memory-progenitor phenotypes of human CD22 CAR T cells without diminishing cytotoxicity. RNA sequencing of STAT5i-expanded CD8⁺ T cells confirmed reinforcement of stem-like transcriptional programs and reduced enrichment of effector and exhausted signatures. Together, these findings identify the IL-2Rβ–STAT5 axis as a regulator of CD8⁺ T-cell differentiation and support transient STAT5 modulation during ex vivo expansion as a strategy to improve therapeutic T-cell products.

This dataset

Open GSE335822 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE335822_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1479656 and SRA study SRP710605. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

5 conditions, mostly in triplicate

Naive ×3 IL2 ×3 IL2S5i ×3 IL15 ×3 IL15S5i ×3

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 15 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9821659 Naive 1 Naive
GSM9821660 Naive 2 Naive
GSM9821661 Naive 3 Naive
GSM9821662 IL2 1 IL2
GSM9821663 IL2 2 IL2
GSM9821664 IL2 3 IL2
GSM9821665 IL2S5i 1 IL2S5i
GSM9821666 IL2S5i 2 IL2S5i
GSM9821667 IL2S5i 3 IL2S5i
GSM9821668 IL15 1 IL15
GSM9821669 IL15 2 IL15
GSM9821670 IL15 3 IL15
GSM9821671 IL15S5i 1 IL15S5i
GSM9821672 IL15S5i 2 IL15S5i
GSM9821673 IL15S5i 3 IL15S5i

Datasets on a similar topic

GSE271367 Enhancing tumor response to adoptive T cell therapy by targeting PHD2/3 in CD8 T cells 18 samples shares cd8, adoptive, therapy
GSE277610 Endothelial PD-L1 brakes CD8+ T cell exhaustion, empowering anti-tumor immunity in non-small cell lung cancer 17 samples shares cd8, exhaustion
GSE269347 Daunorubicin-induced T cell remodeling facilitates a high antitumor response to PD-1 blockade therapy by promoting the expansion and effector function of CD8+ prolifeating T cells [scRNA-Seq] 16 samples shares cd8, therapy
GSE320177 All -trans retinoic acid suppresses CD8+ T cell terminal exhaustion which enhances anti–PD-1 efficacy against glioblastoma [RNA-Seq] 12 samples shares cd8, exhaustion
GSE207029 Blockade of avb8 integrin synergizes with checkpoint inhibition to enhance anti-tumor immunity through Cxcl9-dependent augmentation of CD8+ T cell cytotoxicity 12 samples shares cd8, inhibition
GSE304763 A pan-immunotherapy signature to predict intratumoral CD8+ T cell expansions [scTCR_immunotherapies] 91 samples shares cd8, therapy
GSE223164 Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor 49 samples shares cd8, exhaustion
GSE274865 Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy [CUT&Tag] 36 samples shares cd8, therapy

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.