{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE254nnn/GSE254341/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":[" Mus musculus","Homo sapiens"],"gds_type":["Methylation profiling by high throughput sequencing"," Genome binding/occupancy profiling by high throughput sequencing"," Expression profiling by high throughput sequencing"," Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254341"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Targeting Nat10 reprograms regulatory T cells function to enhance anti-PD-1 immunotherapy sensitivity in lung cancer","description":"A significant challenge for improving the efficacy of immune checkpoint blockade (ICB) therapy is the concurrent activation of regulatory T (Treg) cells, which can dampen anti-tumor responses. Thus, elucidating the mechanisms that maintain Treg suppressive function within the tumor microenvironment (TME) is critical. Here, we identify an accumulation of N-acetyltransferase 10 (Nat10)-modified RNA, particularly in Nat10⁺ Foxp3⁺ Treg cells, in human non-small cell lung cancer (NSCLC). Genetic ablation of Nat10 in tumor-infiltrating (TI) Treg cells, or pharmacological inhibition of Nat10 expression, significantly reduces the PD-1⁺ Treg/CD8⁺ T cell ratio. These effects are accompanied by an increase in IFNγ⁺ Treg cells, a reduction in the immunosuppressive activity of Treg cells, and inhibition of tumor progression. Mechanistically, Nat10 promotes TI Treg cell infiltration and activation independently of its RNA-modifying function by directly interacting with Foxp3 and chromatin, shaping 3D genome architecture. Combined administration of anti-PD-1 antibodies and a Nat10 inhibitor further impairs TI Treg-mediated immunosuppression, leading to enhanced tumor control. Our findings demonstrate that Nat10 is a key regulator of TI Treg cell fragility and function, and that its inhibition may enhance the therapeutic efficacy of ICB.","dates":{"publication":"2026/08/21"},"accession":"GSE254341","cross_references":{"GSM":["GSM8038005","GSM8038004","GSM8038003","GSM8038022","GSM8038021","GSM8038020","GSM9092579","GSM9092578","GSM9092577","GSM8038009","GSM9092576","GSM8038008","GSM9092575","GSM8038007","GSM8038006","GSM9092583","GSM9092582","GSM9092581","GSM9092580","GSM8038016","GSM8038015","GSM8038014","GSM8038013","GSM8038012","GSM8038011","GSM8038010","GSM9872194","GSM9872193","GSM9872196","GSM9872195","GSM9872198","GSM9092586","GSM9872197","GSM8038019","GSM8038018","GSM9092585","GSM9092584","GSM9872199","GSM8038017","GSM9872192"],"GPL":["24676","24247"],"GSE":["254341"],"taxon":[" Mus musculus","Homo sapiens"]}}