{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289055/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289055"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"P2RY2 fuelled by eATP drives cancer immune evasion and therapy resistance","description":"In this study, we identify P2RY2 as a pivotal upstream driver of both PGE2 accumulation and B7-H3 upregulation in the TME. This process is fuelled by extracellular ATP (eATP), a cognate ligand for P2RY2 that is commonly and markedly elevated in the TME and rises further under immunotherapies. Genetic or pharmacological disruption of P2RY2 substantially reduces intratumoural PGE2 and B7-H3, increasing T cell infiltration, effector functions, proliferation, and persistence within the TME. Consequently, targeting P2RY2 substantially improves the efficacy of TCR-engineered T cells, CAR-T cells, and immune checkpoint blockade (ICB) in multiple syngeneic and humanized mouse tumour models, and potentiates patient-derived tumour-infiltrating lymphocytes (TILs) against paired primary tumour cells. By establishing P2RY2 as the crucial link between eATP and tumour-induced immunosuppression, our study reveals how a receptor typically associated with innate “danger” signalling can be hijacked to undermine adaptive immunity, thereby providing a promising therapeutic avenue to overcome a common immune resistance mechanism in cancer and advance T cell–based cancer therapies.","dates":{"publication":"2026/07/07"},"accession":"GSE289055","cross_references":{"GSM":["GSM8782700","GSM8782689","GSM8782688","GSM8782699","GSM8782685","GSM8782696","GSM8782684","GSM8782695","GSM8782687","GSM8782698","GSM8782697","GSM8782686","GSM8782692","GSM8782691","GSM8782694","GSM8782683","GSM8782693","GSM8782690"],"GPL":["24676"],"GSE":["289055"],"taxon":["Homo sapiens"],"PMID":["[42392075]"]}}