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Cell surface-targeted immunocytokines program systemic anti-tumor immunity

GSE252949 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2024/07/07 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 × Ag+ CD8 T cells, PBS, vs 5 × Ag+ CD8 T cells, IgG-Cyt, vs 5 × Ag+ CD8 T cells, aCD45-Cyt,Groups 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
Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunityNature immunology · 2024
Summary (written by the submitters)
Systemically-administered cytokines are potent immunotherapy agents but exhibit severe dose-limiting toxicities. To overcome this challenge, cytokines have been engineered for intratumoral retention following local delivery. However, despite inducing regression of treated lesions, tumor-localized cytokines often elicit only modest abscopal effects at distal untreated tumors.
Read the full summary ↓
Here we report a localized cytokine therapy that safely elicits potent systemic anti-tumor immunity by engineered targeting of the ubiquitous leukocyte receptor CD45. CD45-targeted immunocytokines (αCD45-Cyt) exhibit significantly diminished internalization rates relative to their wild-type counterparts; this prolonged surface retention sustains downstream pSTAT induction and enables both cis and trans signaling between lymphocytes. Intratumoral αCD45-Cyt administration led to decoration of leukocytes in the tumor and tumor-draining lymph node (TDLN) without systemic exposure. Therapeutically, a single dose of αCD45-IL12 followed by a single dose of αCD45-IL15 eradicated both treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models. Mechanistically, prolonged exposure to αCD45-Cyt in the tumor and TDLN reprogrammed CD8+ T cells in the TDLN to exhibit an anti-viral transcriptional signature and expanded tumor-specific effector T cells in both the tumor and TDLN. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy.
Published in
Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity
Santollani L, Maiorino L, Zhang YJ et al. · Nature immunology 2024 · PMID 39112631 · doi:10.1038/s41590-024-01925-7
This dataset
Open GSE252949 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 GSE252949_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 PRJNA1063299 and SRA study SRP482954. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39112631) ↗
Study design
5 × Ag+ CD8 T cells, PBS, vs 5 × Ag+ CD8 T cells, IgG-Cyt, vs 5 × Ag+ CD8 T cells, aCD45-Cyt,

Supports a between-group comparison across 15 samples.

How we read this: 3 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
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