{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333360"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Distinct neuroinflammatory effects of individual chemotherapeutics shape chemotherapy-induced peripheral neuropathy in a novel mouse model of CVAD combination regimen.","description":"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.","dates":{"publication":"2026/05/31"},"accession":"GSE333360","cross_references":{"GSM":["GSM9761484","GSM9761485","GSM9761483","GSM9761503","GSM9761504","GSM9761501","GSM9761502","GSM9761488","GSM9761500","GSM9761489","GSM9761486","GSM9761487","GSM9761495","GSM9761496","GSM9761493","GSM9761494","GSM9761491","GSM9761492","GSM9761490","GSM9761512","GSM9761510","GSM9761499","GSM9761511","GSM9761497","GSM9761498","GSM9761509","GSM9761507","GSM9761508","GSM9761505","GSM9761506"],"GPL":["24247"],"GSE":["333360"],"taxon":["Mus musculus"]}}