GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328069/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328069GEOGSEfalseImmune Context Governs Stage-Specific Responses to Depleting Anti-PD-1 Antibody in Type 1 DiabetesA depleting anti-PD-1 antibody (D-aPD-1) exhibits striking stage-dependent effects in a mouse model of T1D: delaying hyperglycemia onset in early insulitis (E-insulitis) but paradoxically accelerating disease in late insulitis (L-insulitis). Compared with E-insulitis, L-insulitis pancreatic islets show elevated immune cell infiltration, a pronounced Teff/Treg imbalance, and enrichment of proinflammatory macrophages—features that partially mirror human T1D pathology. Comprehensive analyses of the islet immune microenvironment identified macrophages as the primary mediators underlying these divergent therapeutic outcomes. Specifically, D-aPD-1 markedly enhances macrophage accumulation, FcgR expression, and the activation of IFN-a/g and TNF-a response pathways. The antibody further amplifies macrophage production of proinflammatory cytokines and chemokines. Among macrophage subsets, Mac-3 predominantly mediates these responses to D-aPD-1. Collectively, proinflammatory macrophages and their interactions with D-aPD-1 are critically determinants of therapeutic outcome.2026/09/23GSE328069GSM9671810GSM9671813GSM9671812GSM967181124247328069Mus musculus[42746516]