GEO series

Glutamine antagonist JHU083 reprograms immunosuppressive tumor-associated macrophages to drive tumor immunity in urologic cancers, bulk RNA-seq

GSE229222 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/05/18 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 6 × Control, TAMs, mouse vs 6 × JHU083, TAMs, mouseGroups 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.
Paper: Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder CancersCancer immunology research · 2024

Summary (written by the submitters)

Glutamine metabolism in the tumor microenvironment is emerging as a critical regulator of immune-mediated anti-tumor responses. We report potent tumor growth inhibition by the glutamine antagonist prodrug JHU083 in urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes (TIMs). Using orthogonal approaches, we show that JHU083-mediated glutamine antagonism in the tumor microenvironment induces TNF, inflammatory, and mTORC1 signaling in different intra-tumoral TAM clusters.

Read the full summary ↓

Additionally, we report that JHU083 increases proliferation in tissue-resident macrophages intratumorally and in different TAM sub-clusters. Functionally, we report that JHU083-reprogrammed TAMs have increased tumor cell phagocytosis and diminished pro-angiogenic capacities. In vivo inhibition of glutamine consumption in TAMs results in increased glycolysis, broken TCA cycle, and disruption in purine metabolism. Although the effect of glutamine antagonism was less profound on tumor-infiltrating T cells for their anti-tumor activity, it promoted a stem cell-like phenotype in CD8+ T cells and decreased the CD4+ Treg abundance. Additionally, we report that JHU083 causes a global shutdown in glutamine utilizing metabolic pathways in tumor cells, leading to reduced HIF-1, c-MYC phosphorylation, and induction of tumor cell apoptosis, all key anti-tumoral features.

Published in

Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers

Praharaj M, Shen F, Lee AJ et al. · Cancer immunology research 2024 · PMID 38701369 · doi:10.1158/2326-6066.CIR-23-1105

This dataset

Open GSE229222 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 GSE229222_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 PRJNA953423 and SRA study SRP431524. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38701369) ↗

Study design

6 × Control, TAMs, mouse vs 6 × JHU083, TAMs, mouse

Supports a between-group comparison across 12 samples.

How we read this: 2 replicated groups read from 12 sample titles; they account for 12 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

GSM7157129 Control, TAMs, mouse 951 Control, TAMs, mouse
GSM7157130 Control, TAMs, mouse 953 Control, TAMs, mouse
GSM7157131 Control, TAMs, mouse 954 Control, TAMs, mouse
GSM7157132 Control, TAMs, mouse 959 Control, TAMs, mouse
GSM7157133 Control, TAMs, mouse 961 Control, TAMs, mouse
GSM7157134 Control, TAMs, mouse 962 Control, TAMs, mouse
GSM7157135 JHU083, TAMs, mouse 955 JHU083, TAMs, mouse
GSM7157136 JHU083, TAMs, mouse 956 JHU083, TAMs, mouse
GSM7157137 JHU083, TAMs, mouse 957 JHU083, TAMs, mouse
GSM7157138 JHU083, TAMs, mouse 958 JHU083, TAMs, mouse
GSM7157139 JHU083, TAMs, mouse 963 JHU083, TAMs, mouse
GSM7157140 JHU083, TAMs, mouse 964 JHU083, TAMs, mouse

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