GEOTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333360GEOGSEfalseDistinct neuroinflammatory effects of individual chemotherapeutics shape chemotherapy-induced peripheral neuropathy in a novel mouse model of CVAD combination regimen.Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting toxicity of cancer treatment for which no disease-modifying therapies exist. Vincristine-induced neuropathy has been linked to neuroimmune activation and interleukin-1 (IL-1) signaling; however, vincristine is almost exclusively administered as part of combination chemotherapy regimens, where the relevance of IL-1–dependent mechanisms remains poorly defined. Here we investigate the role of IL-1 receptor (IL-1R) signaling in neuropathy induced by vincristine alone and by the standard CVAD regimen (cyclophosphamide, vincristine, doxorubicin and dexamethasone) in male C57BL6/J mice. IL-1R blockade with the clinically approved antagonist anakinra prevented vincristine-induced mechanical hypersensitivity and attenuated established vincristine-induced peripheral neuropathy, without adverse effects on motor function, hematological parameters or body weight. Additionally, we established a novel CVAD-induced neuropathy model and demonstrate that anakinra partially attenuated CVAD-induced mechanical hypersensitivity and preserved motor function without exacerbating systemic toxicity. Dissection of individual CVAD components identified vincristine as the dominant driver of grip strength decline and IL-1–dependent neuroinflammatory signaling, whereas cyclophosphamide and doxorubicin contributed to sensory hypersensitivity through largely IL-1R–independent mechanisms, and dexamethasone did not induce sensory neuropathy. Immunohistochemistry and transcriptome profiling of peripheral nervous tissue revealed distinct, time-dependent and agent-specific neuroimmune responses with distinct inflammatory and immunosuppressive effects shaping the net CVAD neuroinflammatory phenotype. Together, these findings redefine CIPN as an emergent property of combination chemotherapy and establish IL-1R signaling as a context-dependent therapeutic target with translational relevance.2026/05/31GSE333360GSM9761484GSM9761485GSM9761483GSM9761503GSM9761504GSM9761501GSM9761502GSM9761488GSM9761500GSM9761489GSM9761486GSM9761487GSM9761495GSM9761496GSM9761493GSM9761494GSM9761491GSM9761492GSM9761490GSM9761512GSM9761510GSM9761499GSM9761511GSM9761497GSM9761498GSM9761509GSM9761507GSM9761508GSM9761505GSM976150624247333360Mus musculus