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Immune hallmarks of recurrent immune checkpoint inhibitor-mediated inflammatory arthritis

GSE338460 Homo sapiens Expression profiling by high throughput sequencing; Other 25 samples Submitted 2026/07/25 Platform GPL24676
Summary
Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (ICI-IA). However, the mechanisms underlying ICI-IA, especially its recurrence, have not been fully investigated. The purpose of this study is to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal synovial fluid (SF) samples. SF samples were collected from six ICI-IA patients at the first and second occurrences of ICI-IA and analyzed with single-cell RNA sequencing (scRNAseq) (n=3), scTCRseq (n=3), scBCRseq (n=3), and flow cytometry (n=6). SF samples from cancer-naïve osteoarthritis patients (n=6) were used as negative controls. Analysis revealed that effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells were enriched in the SF of ICI-IA patients. Ninety three percent and fifty percent of the top ten expanded clones of effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells, respectively, were shared between the first and second ICI-IA flare. These top clones were characterized by the production of pro-inflammatory type 1 cytokines including IFNg, TNFa, and IL-21, especially in the second flare, suggesting immune memory responses to cognate antigen. Cell-cell communication analysis suggests that effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells interacted with each other and with myeloid cells and B cells through chemokines (CXCL9/10/11/13, CCL3) and cytokines (MIF, IL-2/7/15/21). Overall, longitudinal SF analysis from ICI-IA patients for the first time revealed the expansion of effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells with type 1 cytokine signatures that potentially contribute to development or recurrence of ICI-IA.
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Direct links to NCBI, no account and no request form: the whole study as GSE338460_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 25 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1494521 and SRA study SRP717645. Searching any of these in the dataset finder brings you back here.

Study design
25 conditions, each sampled once — no replicated groups

Read from 25 sample titles: 25 distinct titles with little repetition. Check it against the sample list below before relying on it.

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