GEO series

Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade

GSE310740 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/01/06 Platform GPL30172

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 5 × 95P vs 4 × 78 vs 4 × 95 vs 3 × 78PGroups 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: Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockadeScience immunology · 2026

Summary (written by the submitters)

CAR-T therapy has shown limited synergy with PD-1/PD-L1 blockade, but the mechanisms underlying resistance remain unclear. PD-1⁺TCF1⁺ stem-like T cells mediate responses to PD-1/PD-L1 blockade and are maintained by MHC-dependent interactions with DCs in tumor-draining lymph nodes (dLN). Because CAR-Ts recognize intact antigen, not peptide-MHC, their activation is confined to tumors, potentially preventing maintenance of this critical subset.

Read the full summary ↓

In ROR1⁺ lung cancer models, ROR1-targeting CAR-Ts rapidly down-regulated TCF1, became exhausted, and were not enhanced by PD-L1 blockade. Overexpression of the AP-1 transcription factor c-Jun, but not BATF, enabled formation of PD-1⁺TCF1⁺ reservoirs in tumors, not dLN, but did not prevent exhaustion, as PD-1 induced post-transcriptional c-Jun down-regulation. Remarkably, PD-L1 blockade restored c-Jun levels, dramatically increased CAR-Ts, and enabled near-complete ROR1+ tumor clearance. These findings identify PD-1 as a suppressor of c-Jun and reveal that MHC-independent CAR-Ts can be engineered to establish intratumoral stem-like reservoirs that overcome resistance to PD-1 blockade.

Published in

Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade

Snyder AJ, Garrison SM, Kluesner MG et al. · Science immunology 2026 · PMID 41790934 · doi:10.1126/sciimmunol.adw7685

This dataset

Open GSE310740 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 GSE310740_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 PRJNA1367011 and SRA study SRP647615. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41790934) ↗

Study design

5 × 95P vs 4 × 78 vs 4 × 95 vs 3 × 78P

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM9307792 78_1393 78
GSM9307793 78_1339 78
GSM9307794 78_1487 78
GSM9307795 78_1490 78
GSM9307796 78P_1396 78P
GSM9307797 78P_1496 78P
GSM9307798 78P_1486 78P
GSM9307799 95_1462 95
GSM9307800 95_1392 95
GSM9307801 95_1499 95
GSM9307802 95_1419 95
GSM9307803 95P_1473 95P
GSM9307804 95P_1362 95P
GSM9307805 95P_1474 95P
GSM9307806 95P_1485 95P
GSM9307807 95P_1455 95P

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GSE310251 Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade 33 samples shares car-t, ap-1, pd-1, intratumoral, modulating, resistance, establish, stem-like
GSE310250 Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade 15 samples shares car-t, ap-1, pd-1, intratumoral, modulating, resistance, establish, stem-like
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GSE285965 Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite [Peritoneum] 24 samples shares pd-1, modulating
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