GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311343/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311343GEOGSEfalseChemotherapeutic Induction of Single-Stranded DNA Accumulation Sensitizes Triple-Negative Breast Cancer to ImmunotherapyDespite 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.2026/06/20GSE311343GSM9323821GSM9323820GSM9323824GSM9323823GSM9323822GSM932381924247311343Mus musculus