GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345439/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345439GEOGSEfalseTumor-Associated Senescent Non-Classical Monocytes Promote Immune Suppression and Progression of Advanced Prostate Cancer [CUT&Run]Prostate cancer, a leading cause of male cancer mortality, poses major therapeutic hurdles due to its immunosuppressive tumor microenvironment (TME). We link MYC amplification and PTEN deletion to metastatic prostate adenocarcinoma and identify a specific population of tumor-associated non-classical monocytes (staNC-Mo, CD11b+Ly6cLowCD14HiCD43LowCX3CR1Low) as key mediators of immune suppression. MYC overexpression with Pten loss induces mitochondrial stress, triggering tumor-cell apoptosis and HSP60 release. The HSP60/TLR4 signaling activates staNC-Mo to secrete TNF-α, stimulating endothelial G-CSF production and driving staNC-Mo differentiation in bone marrow and spleen. CD14-dependent phagocytosis of apoptotic tumor cells drives staNC-Mo senescence and TGF-β1 secretion. TGF-β1 activates PI3K/AKT signaling in tumor cells, inducing CXCL5 secretion and reinforcing staNC-Mo recrutiment. Senescent staNC-Mo also release IL-18, suppressing innate and adaptive immunity. Targeting Ly6c, CD14, CXCL5-CXCR2, TLR4, or IL-18 reduces staNC-Mo accumulation, relieves TME immunosuppression, and inhibits tumor progression, suggesting therapeutic strategies for advanced prostate cancer.2026/09/02GSE345439GSM10003502GSM10003503GSM10003498GSM10003499GSM10003500GSM1000350137305345439Mus musculus