GEO series
Cytotoxic CD39+ tumor-associated NK cells respond to NKG2A blockade in lung cancer (10X Multiome)
GSE304741
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing
22 samples
Submitted 2026/06/05
Platform GPL24676
Summary
Natural killer (NK) cell–targeting immunotherapies are emerging, yet the differentiation and functional states of tumor-infiltrating NK cells remain poorly understood. Using matched single-nucleus RNA and ATAC sequencing of samples from patients with non–small cell lung cancer (NSCLC), we resolved the transcriptional and epigenetic landscape of intratumoral NK cells. We identified two tumor-associated NK (taNK) cell subsets marked by expression of ITGAE (CD103) and ITGA1 (CD49a) that display features of tissue residency and dysfunction while preserving cytotoxic function. Trajectory and regulon analyses revealed an inflammation-driven transition from early granzyme K (GZMK)+ NK cells toward an ENTPD1+ (CD39+) effector state characterized by interferon-stimulated gene (ISG) programs. Functional profiling established CD39+ taNK cells as the dominant cytotoxic NK cell population with superior killing capacity that was further potentiated by NKG2A blockade. This study offers mechanistic insights into NK cell differentiation in NSCLC and establishes CD39+ taNK cells as a targetable effector population for immunotherapy.
Published in
Serger C, Rebuffet L, Sandholzer MT et al.
· Science immunology 2026
· PMID 42247486
· doi:10.1126/sciimmunol.aeb6645
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE304741_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 22 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1302431. Searching any of these in the dataset finder brings you back here.
Study design
11 × CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, vs 11 × CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC,
Supports a between-group comparison across 22 samples.
2 replicated groups read from 22 sample titles; they account for 22 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9156070 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 1
- GSM9156071 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 1
- GSM9156072 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 2
- GSM9156073 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 2
- GSM9156074 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 3
- GSM9156075 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 3
- GSM9156076 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 4
- GSM9156077 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 4
- GSM9156078 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 5
- GSM9156079 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 5
- GSM9156080 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 6
- GSM9156081 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 6
- GSM9156082 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 7
- GSM9156083 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 7
- GSM9156084 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 8
- GSM9156085 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 8
- GSM9156086 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 9
- GSM9156087 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 9
- GSM9156088 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 10
- GSM9156089 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 10
- GSM9156090 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, GEX, rep 11
- GSM9156091 CD56⁺ NK and T cells sorted from treatment-naive NSCLC, ATAC, rep 11
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