2026-10-13T18:56:21Z https://www.scidb.cn/oai

10.57760/sciencedb.29300 2025-08-22T17:27:01Z

2025-08-22 Pathogenic CD137+ IL-17+ atypical Treg is a unique feature of immune checkpoint inhibitor-induced inflammatory arthritis and is abrogated by IL-6R blockade doi:10.57760/sciencedb.29300 en Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear. Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population co-expressing CD137 and IL-6R (AtpTreg). These cells exhibited reduced immunosuppressive capacity while aberrantly producing high level of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival. Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity. Our findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation. cross-compartment longitudinal sampling; clinical follow-up assessment; single-cell multi-omics; Inflammatory arthritis after checkpoint blockade Yifei Ma RESTRICTED dataset Science Data Bank