{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309310/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309310"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Reversion of T cell exhaustion enables cancer vaccine efficacy in BRCA1-deficient ovarian cancer","description":"Background: BRCA mutations in ovarian cancer (OC) are associated with increased tumor-infiltrating lymphocytes and inflammatory features, yet immunotherapy for OC has failed to meet expectations. This study hypothesizes that BRCA1 or BRCA2 deficiency differently influences the response to cancer vaccine. Methods: We used the syngeneic orthotopic ID8 mouse ovarian tumor models deficient for Trp53, Trp53 and Brca1, or Trp53 and Brca2. Tumor-implanted mice were vaccinated with a dendritic cell-based whole tumor lysate vaccine (termed OCDC) alone or in combination with anti-VEGF therapy, PARP inhibitor, and/or anti-PD-1 immune checkpoint inhibitor. Tumor burden, mice survival and monitoring of T cell responses were evaluated by bioluminescence imaging, flow cytometry and interferon gamma (IFNg)-ELISpot assay. Transcriptomic profiling of tumor cell and immune cell-compartments was performed using NanoString GeoMx digital spatial profiling. Results: Brca1 deficiency—but not Brca2— impairs effectiveness of OCDC vaccine. OCDC vaccine reduced tumor growth rates and improved survival of mice implanted with Trp53-/- and Trp53-/-Brca2-/-ID8 tumors, but was ineffective in mice implanted Trp53-/-Brca1-/- tumor model. Transcriptomic analysis revealed that tumors responsive to OCDC (Brca wild-type or Brca2-/-) underwent metabolic and immunologic reprogramming post-vaccination, unlike Brca1-/- tumors. Inefficacy of the cancer vaccine was driven by a tumor microenvironment that was already inflamed, characterized by a high level of activated yet exhausted T cells, which hinder additional immune activation by vaccination. Combining OCDC with anti-VEGF and PARP inhibitors partially overcame vaccine resistance in Brca1-/- tumors, while adding anti-PD-1 further improved vaccine effectiveness by boosting T cell activity and promoting long-term survival. Conclusion: These findings highlight BRCA1’s role in cancer vaccine sensitivity and support using rational combinations to overcome vaccine inefficacy in BRCA1-mutated OC.","dates":{"publication":"2026/06/09"},"accession":"GSE309310","cross_references":{"GSM":["GSM9265092","GSM9265093","GSM9265094","GSM9265095","GSM9265096","GSM9265097","GSM9265098","GSM9265099","GSM9265090","GSM9265091","GSM9265081","GSM9265082","GSM9265083","GSM9265084","GSM9265085","GSM9265086","GSM9265087","GSM9265088","GSM9265089","GSM9265080","GSM9265191","GSM9265070","GSM9265071","GSM9265192","GSM9265072","GSM9265193","GSM9265194","GSM9265073","GSM9265074","GSM9265195","GSM9265075","GSM9265196","GSM9265197","GSM9265076","GSM9265077","GSM9265198","GSM9265078","GSM9265199","GSM9265079","GSM9265190","GSM9265180","GSM9265060","GSM9265181","GSM9265061","GSM9265182","GSM9265062","GSM9265183","GSM9265063","GSM9265184","GSM9265185","GSM9265064","GSM9265065","GSM9265186","GSM9265066","GSM9265187","GSM9265188","GSM9265067","GSM9265068","GSM9265189","GSM9265069","GSM9265170","GSM9265171","GSM9265050","GSM9265051","GSM9265172","GSM9265052","GSM9265173","GSM9265174","GSM9265053","GSM9265054","GSM9265175","GSM9265055","GSM9265176","GSM9265177","GSM9265056","GSM9265057","GSM9265178","GSM9265058","GSM9265179","GSM9265059","GSM9265160","GSM9265040","GSM9265161","GSM9265162","GSM9265041","GSM9265042","GSM9265163","GSM9265043","GSM9265164","GSM9265165","GSM9265044","GSM9265045","GSM9265166","GSM9265046","GSM9265167","GSM9265168","GSM9265047","GSM9265048","GSM9265169","GSM9265049","GSM9264739","GSM9264859","GSM9264738","GSM9264979","GSM9264737","GSM9264858","GSM9264736","GSM9264857","GSM9264978","GSM9264856","GSM9264977","GSM9264735","GSM9264976","GSM9264734","GSM9264855","GSM9264865","GSM9264744","GSM9264986","GSM9264985","GSM9264743","GSM9264864","GSM9264742","GSM9264863","GSM9264984","GSM9264862","GSM9264983","GSM9264741","GSM9264982","GSM9264740","GSM9264861","GSM9264860","GSM9264981","GSM9264980","GSM9264729","GSM9264728","GSM9264849","GSM9264727","GSM9264848","GSM9264969","GSM9264968","GSM9264726","GSM9264847","GSM9264725","GSM9264846","GSM9264967","GSM9264845","GSM9264966","GSM9264724","GSM9264965","GSM9264723","GSM9264844","GSM9264733","GSM9264854","GSM9264975","GSM9264853","GSM9264974","GSM9264732","GSM9264731","GSM9264852","GSM9264973","GSM9264730","GSM9264851","GSM9264972","GSM9264850","GSM9264971","GSM9264970","GSM9264719","GSM9264839","GSM9264718","GSM9264959","GSM9264717","GSM9264838","GSM9264716","GSM9264837","GSM9264958","GSM9264836","GSM9264957","GSM9264715","GSM9264956","GSM9264714","GSM9264835","GSM9264713","GSM9264834","GSM9264955","GSM9264833","GSM9264954","GSM9264712","GSM9264722","GSM9264843","GSM9264964","GSM9264842","GSM9264963","GSM9264721","GSM9264962","GSM9264720","GSM9264841","GSM9264840","GSM9264961","GSM9264960","GSM9264709","GSM9264708","GSM9264829","GSM9264707","GSM9264828","GSM9264949","GSM9264948","GSM9264706","GSM9264827","GSM9264705","GSM9264947","GSM9264826","GSM9264704","GSM9264825","GSM9264946","GSM9264945","GSM9264703","GSM9264824","GSM9264702","GSM9264823","GSM9264944","GSM9264822","GSM9264943","GSM9264701","GSM9264711","GSM9264832","GSM9264953","GSM9264710","GSM9264831","GSM9264952","GSM9264830","GSM9264951","GSM9264950","GSM9264819","GSM9264939","GSM9264818","GSM9264817","GSM9264938","GSM9264816","GSM9264937","GSM9264936","GSM9264815","GSM9264814","GSM9264935","GSM9264813","GSM9264934","GSM9264933","GSM9264812","GSM9264811","GSM9264932","GSM9264942","GSM9264700","GSM9264821","GSM9264820","GSM9264941","GSM9264940","GSM9264809","GSM9264808","GSM9264929","GSM9264928","GSM9264807","GSM9264806","GSM9264927","GSM9264805","GSM9264926","GSM9264925","GSM9264804","GSM9264803","GSM9264924","GSM9264802","GSM9264923","GSM9264922","GSM9264801","GSM9264800","GSM9264921","GSM9264810","GSM9264931","GSM9264930","GSM9264919","GSM9264918","GSM9264917","GSM9264916","GSM9264915","GSM9264914","GSM9264913","GSM9264912","GSM9264911","GSM9264910","GSM9264920","GSM9264909","GSM9264908","GSM9264907","GSM9264906","GSM9264905","GSM9264904","GSM9264903","GSM9264902","GSM9264901","GSM9264900","GSM9264699","GSM9264789","GSM9264799","GSM9264798","GSM9264797","GSM9264796","GSM9264795","GSM9264794","GSM9264793","GSM9264792","GSM9264791","GSM9264790","GSM9264779","GSM9264899","GSM9264778","GSM9264788","GSM9264787","GSM9264786","GSM9264785","GSM9264784","GSM9264783","GSM9264782","GSM9264781","GSM9264780","GSM9264769","GSM9264768","GSM9264889","GSM9264767","GSM9264888","GSM9264777","GSM9264898","GSM9264776","GSM9264897","GSM9264896","GSM9264775","GSM9264774","GSM9264895","GSM9264773","GSM9264894","GSM9264893","GSM9264772","GSM9264771","GSM9264892","GSM9264770","GSM9264891","GSM9264890","GSM9264759","GSM9264879","GSM9264758","GSM9264999","GSM9264757","GSM9264878","GSM9264756","GSM9264877","GSM9264998","GSM9264766","GSM9264887","GSM9264765","GSM9264886","GSM9264885","GSM9264764","GSM9264763","GSM9264884","GSM9264762","GSM9264883","GSM9264882","GSM9264761","GSM9264760","GSM9264881","GSM9264880","GSM9264749","GSM9264748","GSM9264869","GSM9264747","GSM9264868","GSM9264989","GSM9264988","GSM9264746","GSM9264867","GSM9264745","GSM9264866","GSM9264987","GSM9264876","GSM9264997","GSM9264755","GSM9264996","GSM9264754","GSM9264875","GSM9264753","GSM9264874","GSM9264995","GSM9264873","GSM9264994","GSM9264752","GSM9264751","GSM9264872","GSM9264993","GSM9264750","GSM9264871","GSM9264992","GSM9264991","GSM9264870","GSM9264990","GSM9265150","GSM9265151","GSM9265030","GSM9265031","GSM9265152","GSM9265032","GSM9265153","GSM9265154","GSM9265033","GSM9265034","GSM9265155","GSM9265035","GSM9265156","GSM9265157","GSM9265036","GSM9265037","GSM9265158","GSM9265038","GSM9265159","GSM9265039","GSM9265140","GSM9265020","GSM9265141","GSM9265142","GSM9265021","GSM9265022","GSM9265143","GSM9265023","GSM9265144","GSM9265145","GSM9265024","GSM9265025","GSM9265146","GSM9265026","GSM9265147","GSM9265148","GSM9265027","GSM9265028","GSM9265149","GSM9265029","GSM9265130","GSM9265131","GSM9265010","GSM9265011","GSM9265132","GSM9265012","GSM9265133","GSM9265134","GSM9265013","GSM9265014","GSM9265135","GSM9265015","GSM9265136","GSM9265016","GSM9265137","GSM9265017","GSM9265138","GSM9265018","GSM9265139","GSM9265019","GSM9265009","GSM9265240","GSM9265120","GSM9265241","GSM9265000","GSM9265121","GSM9265242","GSM9265122","GSM9265243","GSM9265001","GSM9265002","GSM9265123","GSM9265244","GSM9265245","GSM9265003","GSM9265124","GSM9265125","GSM9265246","GSM9265004","GSM9265005","GSM9265126","GSM9265247","GSM9265248","GSM9265006","GSM9265127","GSM9265128","GSM9265249","GSM9265007","GSM9265008","GSM9265129","GSM9265119","GSM9265230","GSM9265231","GSM9265110","GSM9265111","GSM9265232","GSM9265112","GSM9265233","GSM9265234","GSM9265113","GSM9265114","GSM9265235","GSM9265115","GSM9265236","GSM9265237","GSM9265116","GSM9265117","GSM9265238","GSM9265118","GSM9265239","GSM9265108","GSM9265229","GSM9265109","GSM9265220","GSM9265100","GSM9265221","GSM9265101","GSM9265222","GSM9265102","GSM9265223","GSM9265103","GSM9265224","GSM9265225","GSM9265104","GSM9265105","GSM9265226","GSM9265106","GSM9265227","GSM9265228","GSM9265107","GSM9265218","GSM9265219","GSM9265210","GSM9265211","GSM9265212","GSM9265213","GSM9265214","GSM9265215","GSM9265216","GSM9265217","GSM9265207","GSM9265208","GSM9265209","GSM9265200","GSM9265201","GSM9265202","GSM9265203","GSM9265204","GSM9265205","GSM9265206"],"GPL":["24247"],"GSE":["309310"],"taxon":["Mus musculus"]}}