GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311488/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311488GEOGSEfalseChemotherapeutic Induction of Single-Stranded DNA Accumulation Sensitizes Triple-Negative Breast Cancer to Immunotherapy [scRNA-seq]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.2026/06/20GSE311488GSM9325938GSM9325939GSM9325945GSM9325967GSM9325968GSM9325946GSM9325969GSM9325947GSM9325948GSM9325963GSM9325941GSM9325942GSM9325964GSM9325965GSM9325943GSM9325966GSM9325944GSM9325960GSM9325961GSM9325962GSM9325940GSM9325949GSM9325956GSM9325957GSM9325958GSM9325959GSM9325952GSM9325953GSM9325954GSM9325955GSM9325950GSM932595134328311488Mus musculus