GEO series
Spatial biology reveals macrophage dysfunction in immunosuppressed non-melanoma skin cancer
GSE316922
Homo sapiens
Expression profiling by high throughput sequencing
36 samples
Submitted 2026/08/07
Platform GPL34284
Summary
The rising incidence of non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), particularly among immunosuppressed individuals, underscores the need for a deeper understanding of the tumor microenvironment (TME) to develop effective and safe immunotherapies. This study employed single-cell multi-omic analyses to investigate the spatial distribution and transcriptional profiles of immune cells in NMSC from both immunocompetent (IC) and immunosuppressed (IS) patients. Our results challenge the prevailing notion that immunosuppression is primarily driven by reduced immune cell abundance or lymphocytic dysfunction. We found that IS tumors retain all requisite immune cell populations but display functional suppression and disrupted spatial organization. Our data revealed a limited number of distinct programs, particularly in macrophages and their spatially organized niches, that are linked to restricted T-cell repertoire diversity and impaired clonal expansion, providing a mechanistic bridge between innate dysfunction and adaptive immune failure. These perturbations were further confirmed by a novel spatial epigenomic atlas of the NMSC TME that revealed immune status–specific regulatory programs, including MAF- and ATF3-driven macrophages and CUX1- enriched fibroblast niches, that shape the epigenetic landscape of immunosuppressed tumors. These findings highlight the central role of innate immunity in shaping anti-tumor responses and offer potential therapeutic targets to enhance immunotherapy in this vulnerable patient population.
Published in
Naara S, Kochat V, Rao X et al.
· Cell 2026
· PMID 42556334
· doi:10.1016/j.cell.2026.07.031
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE316922_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 36 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1405546 and SRA study SRP664747. Searching any of these in the dataset finder brings you back here.
Study design
32 × S vs 2 × S132 vs 2 × S144
Supports a between-group comparison across 36 samples.
3 replicated groups read from 36 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9462485 S55
- GSM9462486 S46
- GSM9462487 S54
- GSM9462488 S53
- GSM9462489 S47
- GSM9462490 S51
- GSM9462491 S48
- GSM9462492 S56
- GSM9462493 S49
- GSM9462494 S7
- GSM9462495 S15
- GSM9462496 S17
- GSM9462497 S39
- GSM9462498 S111
- GSM9462499 S118
- GSM9462500 S117
- GSM9462501 S115
- GSM9462502 S138
- GSM9462503 S132_1
- GSM9462504 S132_2
- GSM9462505 S108
- GSM9462506 S143
- GSM9462507 S142
- GSM9462508 S144_1
- GSM9462509 S144_2
- GSM9462510 S114
- GSM9462511 S129
- GSM9462512 S112
- GSM9462513 S128
- GSM9462514 S110
- GSM9462515 S130
- GSM9462516 S75
- GSM9462517 S70
- GSM9462518 S140
- GSM9462519 S131
- GSM9462520 S123
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