GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335494/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335494GEOGSEfalseB-cell depletion improves therapeutic index of combination checkpoint blockade in patients with advanced melanomaCombined 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.2026/08/07GSE335494GSM9814640GSM9814625GSM9814603GSM9814626GSM9814604GSM9814623GSM9814601GSM9814602GSM9814624GSM9814621GSM9814622GSM9814600GSM9814620GSM9814609GSM9814629GSM9814607GSM9814608GSM9814605GSM9814627GSM9814628GSM9814606GSM9814636GSM9814614GSM9814637GSM9814615GSM9814634GSM9814612GSM9814613GSM9814635GSM9814599GSM9814610GSM9814632GSM9814633GSM9814611GSM9814630GSM9814597GSM9814631GSM9814598GSM9814618GSM9814619GSM9814616GSM9814638GSM9814639GSM981461724676335494Homo sapiens[42640721]