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Tumor cell intrinsic type I interferon signaling dictates CD47-SIRPα blockade immunotherapy via metabolic reprograming [dataset 2]

GSE235112 Mus musculus (mouse) RNA-seq (gene expression) 17 samples Submitted 2024/06/04 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 17 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
17 samples: 6 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.
Paper
Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacyNature communications · 2024
Summary (written by the submitters)
Type I interferons (IFN-Is) have been well recognized for their roles in immune cells in tumor immunotherapy. However, their direct effects on tumor cells are less understood. Oxidative phosphorylation (OXPHOS) is typically latent in tumor cells. However, whether OXPHOS can be targeted for immunotherapy remains unclear. Here, we found that tumor cell responsiveness to IFN-Is is essential for CD47-SIRPα blockade immunotherapy.
Read the full summary ↓
Interestingly, IFN-Is directly reprogram tumor cell metabolism by activating OXPHOS for ATP production via ISG15. ATP extracellular release is also enhanced by IFN-Is via autophagy. Tumor cells with a genetic deficiency in OXPHOS or autophagy were resistant to CD47-SIRPα blockade. ATP released upon CD47-SIRPα blockade primes the anti-tumor T cell response via ATP-P2X7 receptor-mediated dendritic cell activation. Further combination with inhibitors of ATP-degrading ectoenzymes, CD39 and CD73, showed synergistic anti-tumor effects. Together, these data reveal the unrecognized mechanisms of IFN-Is on tumor cell metabolic reprograming in tumor immunotherapy and provide novel strategies harnessing this pathway for enhanced efficacy of CD47-SIRPα blockade.
Published in
Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacy
Zhou H, Wang W, Xu H et al. · Nature communications 2024 · PMID 38982116 · doi:10.1038/s41467-024-50136-z
This dataset
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.

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 GSE235112_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA984609 and SRA study SRP444389. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
6h_Medium ×3 24h_Medium ×3 24h_IFNa ×3 48h_Medium ×3 48h_IFNa ×3 6h_IFNa ×2

Supports a between-group comparison across 17 samples.

How we read this: 6 replicated groups read from 17 sample titles; they account for 17 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
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