{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335494/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335494"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"B-cell depletion improves therapeutic index of combination checkpoint blockade in patients with advanced melanoma","description":"Combined checkpoint blockade (CCB) of programmed-death-1 (PD-1) and cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4) is highly active in melanoma but limited by significant morbidity from immune-related adverse events (irAEs). Effective strategies toprevent CCB-mediated irAEs are lacking. Patients with advanced melanoma were randomly assigned to receive standard of care ipilimumab and nivolumab alone (Arm-A: ipi/nivo, n=7) or with one cycle of rituximab (Arm-B; ipi/nivo+rituximab, n=7). Patients receiving ipi/nivo+rituximab experienced lower rates of >grade-3(G3) irAEs (14% versus 57%) and superior G3-irAE-free survival compared to those in ipi/nivo arm (2-year G3- irAE-free survival 86% versus 29% (p=0.01), without adverse impact on tumor regression or survival. Rituximab depleted pre-therapy activated naïve B cells linked to autoimmunity and enhanced CCB-mediated induction of myeloid inflammation and CXCL13+ICOS+ CD4 T cells. B-cell depletion favorably modulates CCB-mediated immune activation and reduces irAE risk.","dates":{"publication":"2026/08/07"},"accession":"GSE335494","cross_references":{"GSM":["GSM9814640","GSM9814625","GSM9814603","GSM9814626","GSM9814604","GSM9814623","GSM9814601","GSM9814602","GSM9814624","GSM9814621","GSM9814622","GSM9814600","GSM9814620","GSM9814609","GSM9814629","GSM9814607","GSM9814608","GSM9814605","GSM9814627","GSM9814628","GSM9814606","GSM9814636","GSM9814614","GSM9814637","GSM9814615","GSM9814612","GSM9814634","GSM9814613","GSM9814635","GSM9814599","GSM9814610","GSM9814632","GSM9814633","GSM9814611","GSM9814630","GSM9814597","GSM9814631","GSM9814598","GSM9814618","GSM9814619","GSM9814616","GSM9814638","GSM9814639","GSM9814617"],"GPL":["24676"],"GSE":["335494"],"taxon":["Homo sapiens"],"PMID":["[42640721]"]}}