{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311488/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311488"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Chemotherapeutic Induction of Single-Stranded DNA Accumulation Sensitizes Triple-Negative Breast Cancer to Immunotherapy [scRNA-seq]","description":"Despite the widespread adoption of chemo-immunotherapy in triple-negative breast cancer (TNBC), how cytotoxic chemotherapy engages antitumor immunity remains poorly defined. Here, we identify cytosolic single-stranded DNA (ssDNA) accumulation as the mechanistic bridge linking genotoxic stress to immune activation. By integrating in vivo TREX1-deficiency transcriptional signatures, we show that ssDNA-driven immunostimulatory programs—rather than TREX1 expression—robustly predict clinical response to chemo-immunotherapy across independent TNBC cohorts. Through a chemotherapeutic screen, we identify LP-184, an acylfulvene-derived alkylating agent in clinical development, as a potent pharmacologic inducer of cytosolic ssDNA and type I interferon signaling. LP-184 enhances antigen presentation, reduces M2-like tumor-suppressive macrophages, and promotes CD8⁺ T-cell priming, thereby synergizing with anti-PD-1 therapy in vivo. These findings redefine the interface between DNA damage and immune activation, establishing ssDNA-driven immune programs as both a predictive biomarker and a therapeutic axis for next-generation chemo-immunotherapy design.","dates":{"publication":"2026/06/20"},"accession":"GSE311488","cross_references":{"GSM":["GSM9325938","GSM9325939","GSM9325945","GSM9325967","GSM9325968","GSM9325946","GSM9325969","GSM9325947","GSM9325948","GSM9325963","GSM9325941","GSM9325942","GSM9325964","GSM9325965","GSM9325943","GSM9325966","GSM9325944","GSM9325960","GSM9325961","GSM9325962","GSM9325940","GSM9325949","GSM9325956","GSM9325957","GSM9325958","GSM9325959","GSM9325952","GSM9325953","GSM9325954","GSM9325955","GSM9325950","GSM9325951"],"GPL":["34328"],"GSE":["311488"],"taxon":["Mus musculus"]}}