GEO series

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

GSE310250 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 15 samples Submitted 2026/01/06 Platform GPL34290

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 15 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Mus musculus (mouse)
Samples: 15 samples: 15 samples, each with a distinct title — no replicated groupsGroups 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 GSE310250 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE310250_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1365632 and SRA study SRP646159. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41790934) ↗

Study design

15 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 15 sample titles: 15 distinct titles with little repetition. 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

GSM9292477 1_IP_SS95_rep1_IgG
GSM9292478 2_IP_SS95_rep2_IgG
GSM9292479 3_IP_SN10_rep1_IgG
GSM9292480 4_IP_SN10_rep2_IgG
GSM9292481 9_IP_SS78_rep1_H3K4me3
GSM9292482 10_IP_SS78_rep2_H3K4me3
GSM9292483 11_IP_SS95_rep1_H3K4me3
GSM9292484 12_IP_SS95_rep2_H3K4me3
GSM9292485 13_IP_SN10_rep1_H3K4me3
GSM9292486 14_IP_SN10_rep2_H3K4me3
GSM9292487 21_IP_SS78_rep1_H3K27me3
GSM9292488 22_IP_SS78_rep2_H3K27me3
GSM9292489 23_IP_SS95_rep1_H3K27me3
GSM9292490 24_IP_SS95_rep2_H3K27me3
GSM9292491 25_IP_SN10_rep1_H3K27me3

Datasets on a similar topic

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
GSE310249 Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade 18 samples shares car-t, ap-1, pd-1, intratumoral, modulating, resistance, establish, stem-like
GSE310740 Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade 16 samples shares car-t, ap-1, pd-1, intratumoral, modulating, resistance, establish, stem-like
GSE288687 Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade 12 samples shares car-t, ap-1, pd-1, intratumoral, modulating, resistance, establish, stem-like
GSE293295 Discovery of BMS-986408, a First-In-Class Dual DGK⍺ and DGK Inhibitor That Unleashes PD-1 Checkpoint and CAR-T Cell Immunotherapies 20 samples shares car-t, pd-1
GSE273488 Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response in mice and humans (RNA-Seq II). 42 samples shares pd-1, establish
GSE285965 Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite [Peritoneum] 24 samples shares pd-1, modulating
GSE261642 PLPP1-deficiency-mediated ferroptosis induced by PD-1 signaling impairs antitumor activity of intratumoral CD8+ T cells I 23 samples shares pd-1, intratumoral

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